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Proceedings, 2019, NPCPT 2019

The 3rd International conference on Natural Products for Cancer Prevention and Therapy

Kayseri, Turkey | 18–20 December 2019

Volume Editor: Mukerrem Betul Yerer Aycan


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Cover Story (view full-size image) Scientific experts from different countries and cities gathered to share their views and experience [...] Read more.
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Plenary Lectures

Open AccessAbstract
Natural Products for Anti-Cancer Progress: The Impact of Artificial Intelligence
Proceedings 2019, 40(1), 37; https://doi.org/10.3390/proceedings2019040037 - 30 Dec 2019
Viewed by 201
Abstract
Finding for more effective anticancer drugs on almost different types of cancer, a huge number of molecules is still under evaluation and barely many more than 100,000 compounds have been tested with researchers and several institutions since recent decades. The fact that plant-derived [...] Read more.
Finding for more effective anticancer drugs on almost different types of cancer, a huge number of molecules is still under evaluation and barely many more than 100,000 compounds have been tested with researchers and several institutions since recent decades. The fact that plant-derived molecules are treated at various levels against cancer is based on a very long history. This has enabled many molecules derived from plant sources to be used in cancer treatment. With the introduction of artificial intelligence, studies on the discovery of new molecules that may be effective in the etiology of various diseases have gained weight as in every field. Artificial intelligence learns the relationship between molecular structure and biological components in certain mathematical algorithms with the obtained in vitro and in vivo values and helps to create new molecular patterns as a result of certain validations. In fact, the artificial intelligence, is now able to develop novel algorithms over the initially defined and further realization might proceed new designs with advanced programming by self-settings new routes through the improvement of desired targets. The introduction of the genetic profile and consequently the discovery of new drug molecules will be one of the most important fields of study of the future. Molecules to be obtained from plant sources will also have very important roles in this direction. Drug therapy for patients with the same disease but with a different genetic profile does not give the same treatment success in every patient. The reason for this is that due to the different mutations in DNA, the protein structures encoded by the genes show differences and the interaction pattern of molecules on the proteins responsible for diseases, could be different. Therefore, for each patient, due to the mutation, diverse molecules that can interact with mutated proteins should be required. This issue is becoming increasingly important all over the world, especially under the name of precision medicine and in the form of personalized drug administration, and demonstrates the importance of drug treatment depending on the individual's genetic profile. It is then useful to treat anticancer molecules of plant origin in this direction. For this purpose, gene rearrangements and gene editing procedures can be applied in plants by using CRISPR technology to improve several factors through leading to design and develop new plant origin molecules for the intended purpose with the assistance of artificial intelligence algorithms. Full article
Open AccessAbstract
Pre-Clinical and Clinical Study Rules for Herbal Medicines
Proceedings 2019, 40(1), 1; https://doi.org/10.3390/proceedings2019040001 - 25 Dec 2019
Viewed by 183
Abstract
Herbal medicines consist of many different type of active ingredients obtained from medicinal plants. The amounts of compounds may be changeable with the environmental, harvesting, draying, storage conditions and process of production as well. In the therapy, efficacy, safety and quality are the [...] Read more.
Herbal medicines consist of many different type of active ingredients obtained from medicinal plants. The amounts of compounds may be changeable with the environmental, harvesting, draying, storage conditions and process of production as well. In the therapy, efficacy, safety and quality are the main properties for both synthetic and natural medicines. Standardized extracts contain certain amount of active ingredient(s) without toxic impurities. Preventive, prophylactic, and curative activities of the standardized extracts are related with their variable chemical constitution. Because of many active ingredients within the herbal products, their toxicity assays, dose-response relationships and clinical trial tests are difficult to follow and not clear. In this review, the impotency of the pre-clinical studies on the herbal products, their standardization and trues/falses/challenges in their clinical trials will be investigated. Full article
Open AccessAbstract
Herbal Products and Supplements in Palliative Care
Proceedings 2019, 40(1), 35; https://doi.org/10.3390/proceedings2019040035 - 27 Dec 2019
Viewed by 219
Abstract
Conventional medicine focuses mostly on the diagnosis and treatment of disease which is the acute localized problem in healthy body. On the other hand, chronic diseases are functional disorders in physiological processes. Therapeutic goal is not to treat the disease but heal the [...] Read more.
Conventional medicine focuses mostly on the diagnosis and treatment of disease which is the acute localized problem in healthy body. On the other hand, chronic diseases are functional disorders in physiological processes. Therapeutic goal is not to treat the disease but heal the whole unhealthy body. The environment, changed with the industrial development, created a new human model, that suffering from stress and biologic damage. And that brought us a new terminology; epigenetics. Today, we are aware of that; the body would help itself for healing if we support. Up to date oncology approach, immuno-oncology is the study and development of treatments that take advantage of the body’s immune system to fight cancer. Nature is the main source to support immune system. There is not enough reliable scientific evidence to use it as a treatment for cancer. Bu it is already a part of supportive and palliative care. Supportive treatment is not secondary to cancer. Scientific studies have shown that humans and other organisms are able to adapt better and survive longer when using these adaptogenic herbs. Treating chemo side effects naturally is a common practice these days and it is supported by strong scientific evidence. Full article
Open AccessAbstract
The Use of Natural Products of Epigenetic Modulators in Anti-Cancer Drug Studies
Proceedings 2019, 40(1), 41; https://doi.org/10.3390/proceedings2019040041 - 31 Dec 2019
Viewed by 243
Abstract
The natural products obtained from plants, bacteria, fungi and marine have been used in the treatment of human diseases throughout the centuries. These compounds of them also interfere with the expression of genes by influencing epigenetic mechanisms. Recent researches showed significant outcomes suggesting [...] Read more.
The natural products obtained from plants, bacteria, fungi and marine have been used in the treatment of human diseases throughout the centuries. These compounds of them also interfere with the expression of genes by influencing epigenetic mechanisms. Recent researches showed significant outcomes suggesting that epigenetic silencing of the main regulatory genesis a sign of cancer onset and its progression. Epigenetic mechanisms that regulate expression of genes without mutation in the DNA are carried through DNA methylation, histone modification, chromatin remodeling and RNA interference. DNA methylation observed in the promoter regions of genes and prevents binding of the transcription factors by suppressing gene expression or by altering the nucleosome package of DNA, and may also directly inhibit transcription. Plant based products, such as curcumin, flavonoids, genistein, have been shown to exhibit cytostatic and apoptotic activities by influencing DNA methylation-based gene expression regulation in tumor cells. Additionally, natural products such as sulforaphane, retinoic acid, cucurbitacin B, casein Q, parthenolide, folate, cobalamin, pyridoxine and methionine also are used as anti-cancer agents based on DNA methylation. On the other hand, microRNAs (miRNAs) play a particular role in the epigenetic regulation of gene expression in post-transcription and post-translation processes. Quercetin, tryptolide, and honokiol are the natural compounds used in miRNA based agents. Histone modifications, which also affect the chromatin structure, play an important role in the initiation and progression of carcinogenesis as well as regulation of gene expression. As expected particular inhibitors of histone acetyltransferases (HATs) and histone deacetylase (HDAC) enzymes which are responsible of histone modifications have been developed for epigenetic intervention in cancer treatment. Numerous natural compounds are known to affect histone-modifying enzymes; such as romidepsin, epigallocatechingallate (EGCG), daidzein, sulphorafane, glucoraphanin, parthenolide, triptolide, sinapinic acid. Natural epigenetic modulators developed for epigenetic mechanisms enable the destruction of apoptotic, necrotic or autophagic pathways of tumor cells. Beside epigenetic mechanisms, these products exert their effects through influencing the cell cycle, DNA repair, and epigenetic mechanisms which modulate gene expression. More extensive in vitro and in vivo studies are required to investigate the effect of natural product-based epigenetic agents which seems to be very promising for future cancer treatment approaches. Full article
Open AccessAbstract
Natural Products in Clinical Trials
Proceedings 2019, 40(1), 32; https://doi.org/10.3390/proceedings2019040032 - 26 Dec 2019
Viewed by 217
Abstract
Herbal medicines are complementary and alternative medicine that is used not only in the treatment of cancer and cancer-related conditions, but also to improve the side effects of anticancer therapies. The use of so‐called alternative medicine has increased over the past 10 years, [...] Read more.
Herbal medicines are complementary and alternative medicine that is used not only in the treatment of cancer and cancer-related conditions, but also to improve the side effects of anticancer therapies. The use of so‐called alternative medicine has increased over the past 10 years, and the use of herbal preparations in clinical trials are growing. Complementary therapies are used by a large number of patients with cancer, particularly those with progressive disease or who have undergone multiple treatments. In 1998, spurred by rising interest in the use of complementary and alternative medicine (CAM) for cancer patients, the National Cancer Institute (NCI) created the Office of Cancer Complementary and Alternative Medicine (OCCAM) and has supported OCCAM with more than $100 million annually since 2005. In the clinical trials official website there are 540 studies were found to be held by extracts whereas 78 studies were found to be held by CAM and 49 studies with marine products by December 2019. The green tea, grape seed, pomegranate, wheat germ, ginger, ginseng root, broccoli sprout, green coffee, Red Reishi, Iscador Q, mistletoe were the most common herbal extracts used in Randomized Clinical Trials (RCT). Curcumin, resveratrol, epigallocathechin gallate, osthole, fiscetin are the samples which are the most common used natural products in RCTs in several cancer types. Prostate, colorectal, breast, lung, head and neck cancers were the most common cancer types where these CAM and natural products were used in RCTs. Increasingly, many researchers have focused their efforts on the potential use of CAMs and natural products and have reevaluated earlier epidemiologic data and initiated clinical trials to determine their potential efficacy as cancer therapy however the pharmacokinetic parameters of these products still need to be widely evaluated by identifying more clinical evidence to be able to use in patients. Full article

Oral Presentations

Open AccessAbstract
Resveratrol Targets Sphingolipid Metabolism and BCR-ABL in Ph+ Acute Lymphoblastic Leukemia to Induce Growth Inhibiton
Proceedings 2019, 40(1), 3; https://doi.org/10.3390/proceedings2019040003 - 25 Dec 2019
Viewed by 179
Abstract
The mechanisms underlying the growth inhibitory effect of resveratrol on Ph+ ALL cells were investigated with regard to targeting of ceramide metabolism and changes in BCR-ABL expression. Growth inhibition and apoptotic effects of resveratrol, SK inhibitor (SKI II), GCS inhibitor (PDMP), SPT inhibitor [...] Read more.
The mechanisms underlying the growth inhibitory effect of resveratrol on Ph+ ALL cells were investigated with regard to targeting of ceramide metabolism and changes in BCR-ABL expression. Growth inhibition and apoptotic effects of resveratrol, SK inhibitor (SKI II), GCS inhibitor (PDMP), SPT inhibitor (myriocin) and resveratrol-inhibitor combinations were investigated by MTT cell proliferation test, Annexin-V/PI staining, caspase-3, PARP expression and cytochrome c release by western blot, while cytostatic effect was investigated by flow cytometry. The effect of resveratrol, inhibitors and combinations on BCR-ABL protein expression was determined by western blot. In addition, the effect of resveratrol on SPT, SK-1/2, GCS protein expression was determined by western blot. In both cell lines resveratrol and resveratrol with SKI II and PDMP suppressed cell growth, triggered apoptosis and arrested the cell cycle at S phase. The combination of resveratrol with myriocin showed cell-specific effects on cell growth and cell cycle, but triggered apoptosis in both cells. In both cell types, resveratrol and combinations generally increased cytochrome-c release, caspase-3 cleavage and PARP cleavage, but cell-specific changes were also detected. Resveratrol decreased the expression of SK-1/SK2 and GCS in both cells and increased SPT expression. While resveratrol, SKI II and PDMP decreased BCR-ABL expression and myriocin increased BCR-ABL expression. Resveratrol together with SKI II and PDMP caused increases in BCR-ABL, while combination with myriocin reduced BCR-ABL expression. As a result, resveratrol suppressed cell growth and triggered apoptosis in Ph+ ALL by regulating ceramide metabolism and BCR-ABL expression. Full article
Open AccessAbstract
Resveratrol Targets Sphingolipid Metabolism to Induce Growth Inhibition in FLT3 ITD Acute Myeloid Leukemia
Proceedings 2019, 40(1), 4; https://doi.org/10.3390/proceedings2019040004 - 25 Dec 2019
Viewed by 205
Abstract
Sphingolipids are important signaling lipids which play crucial roles to determine the cell fate. Ceramide, apoptotic central molecule of sphingolipid metabolism, which is produced through de novo pathway by serine palmitoyl transferase (SPT) and can be converted to antiapoptotic sphingosine-1-phosphate (S1P) and glucosyl [...] Read more.
Sphingolipids are important signaling lipids which play crucial roles to determine the cell fate. Ceramide, apoptotic central molecule of sphingolipid metabolism, which is produced through de novo pathway by serine palmitoyl transferase (SPT) and can be converted to antiapoptotic sphingosine-1-phosphate (S1P) and glucosyl ceramide (GC) by sphingosine kinase (SK) and glucosyl ceramide synthase (GCS), respectively. It is aimed to investigate therapeutic potential of resveratrol on FLT3-ITD (Internal Tandem Duplication) AML cells and to identify potential mechanism behind resveratrol-mediated growth inhibition by targeting of ceramide metabolism. The cytotoxic effects of resveratrol, SPT inhibitor (myricoin), SK-1 inhibitor (SKI II), GCS inhibitor (PDMP), resveratrol: SPT inhibitor, resveratrol: SK-1 inhibitor and resveratrol: GCS inhibitor combinations on MOLM-13 and MV4-11 FLT3 ITD AML cells were investigated by cell proliferation assay. Apoptosis was evaluated by annexin V/PI double staining. There were synergistic cytotoxic effects of resveratrol with co-administration of SPT inhibitor, SK-1 inhibitor and GCS inhibitor and apoptosis was synergistically induced for resveratrol and its combinations. This preliminary data showed for the first time that resveratrol might inhibit the growth of FLT3 ITD AML cells through targeting ceramide metabolism. Full article
Open AccessAbstract
Viburnum opulus L. Fruit Extracts Protect Human Neuroblastoma SH-SY5Y Cells against Hydrogen Peroxide-Induced Cytotoxicity
Proceedings 2019, 40(1), 5; https://doi.org/10.3390/proceedings2019040005 - 25 Dec 2019
Viewed by 199
Abstract
Viburnum L., is one of the most diverse genera of Caprifoliaceae family. There are 4 species of this genus in Turkey. One of them is Viburnum opulus L. The fruits of V. opulus have been used as an antidiabetic in Turkish folk medicine [...] Read more.
Viburnum L., is one of the most diverse genera of Caprifoliaceae family. There are 4 species of this genus in Turkey. One of them is Viburnum opulus L. The fruits of V. opulus have been used as an antidiabetic in Turkish folk medicine and a traditional drink named “gilaburu” in Middle Anatolia. Oxidative stress is involved in the cell degenerative changes in the pathogenesis of a wide variety of human chronic diseases, such as cancer. Some of the studies carried out on the V. opulus extracts revealed the presence of phenolic acids, flavonoids, hydroxybenzoic acids, tannins, coumarins, cathechols, iridoid glycosides, antocyanins, and some others. Most of these polyphenols have various biological activities, including antioxidant, cancer chemopreventive, and anticancer activities. This study aimed to assess the in vitro antioxidant properties of the ethanol extract (VOE), decoction (VOD) and fruit juice (VOFJ) from the fruits of V. opulus against hydrogen peroxide (H2O2)-induced oxidative stress in human SH-SY5Y neuronal cells. Our study revealed that the VOE, VOD and VOFJ provided neuroprotection against H2O2-induced oxidative stress. In conclusion, VOE, VOD and VOFJ can be used as a functional dietary ingredient that might help in reducing health problems associated with various oxidative stress insults. Full article
Open AccessAbstract
In Silico Evaluation of Interactions of Triterpenes in Momordica charantia on Proteins Involved in Angiogenesis
Proceedings 2019, 40(1), 2; https://doi.org/10.3390/proceedings2019040002 - 25 Dec 2019
Viewed by 192
Abstract
Angiogenesis is important process that play active role in tumorigenesis. VEGFR-1, a member of the tyrosine kinase receptor family, is known as the receptor for VEGF ligands in tumor cells. SPARC protein has recently been shown to play a role in metastasis in [...] Read more.
Angiogenesis is important process that play active role in tumorigenesis. VEGFR-1, a member of the tyrosine kinase receptor family, is known as the receptor for VEGF ligands in tumor cells. SPARC protein has recently been shown to play a role in metastasis in various types of cancer. Momordica charantia; is a valuable plant used quite often in traditional medicine. Triterpenes from that plant appear to be promising in in vitro cancer studies. In this study; triterpenes in fruit and seed of M. charantia were selected according to literature. The 3D structure files of triterpenes were obtained from PubChem. The structure files of ligands were prepared with various programs and converted to the appropriate file format. X-ray diffraction structure files of proteins were obtained from RCSB PDB. These structure files were made suitable for molecular docking studies. Docking was performed with the AutoDock Tool (downloaded from autodock.scripps.edu/resources/adt), and the results were scored using the Vina program. According to the in silico analysis; It has been found that various triterpenes which can be obtained from M. charantia can co-inhibit VEGFR-1 and SPARC proteins. These results show that these triterpenes are promising in terms of new therapeutic routes for aggressive cancer therapy. Full article
Open AccessAbstract
The Effect of Kynurenic Acid on Apoptosis in Hepatocellular Carcinoma
Proceedings 2019, 40(1), 6; https://doi.org/10.3390/proceedings2019040006 - 25 Dec 2019
Viewed by 187
Abstract
Kynurenic Acid (KYNA) is a metabolite of tryptophan pathway and also an endogenous antagonist of glutamate receptors. Several studies indicated that glutamate antagonists have anti-proliferative potential. Moreover, subunits of the NMDA receptor which is one of the glutamate receptors have been shown to [...] Read more.
Kynurenic Acid (KYNA) is a metabolite of tryptophan pathway and also an endogenous antagonist of glutamate receptors. Several studies indicated that glutamate antagonists have anti-proliferative potential. Moreover, subunits of the NMDA receptor which is one of the glutamate receptors have been shown to be found in human hepatocellular carcinoma cell line (HepG2). In this study, the antitumor effects of KYNA in HepG2 cells were investigated for the first time at the molecular level. The effects of KYNA on the viability of HepG2 cells were determined by MTT analyses. Effects of KYNA on mRNA transcriptions of apoptosis related genes Bax, Bcl-2 and Caspase-3 were analyzed by qRT-PCR. mRNA expression analysis revealed that the mRNA levels of effector Caspase-3 and pro-apoptotic Bax/Bcl-2 ratio were not increased in HepG2 cells treated with KYNA. In conclusion, our findings showed that KYNA does not exert its anti-proliferative effects on HepG2 cells through caspase-mediated apoptotic cell death, but it may perform this anti-proliferative effect through a different mechanism of death. Further studies are needed to find out potential cell death mechanisms that may play a role in anti-proliferative activity of KYNA on HepG2 cells. Full article
Open AccessAbstract
Antioxidant Capacity of Three Silene Extracts Obtained by Ultrasonication-Assisted Extraction (UAE)
Proceedings 2019, 40(1), 7; https://doi.org/10.3390/proceedings2019040007 - 25 Dec 2019
Viewed by 174
Abstract
Many plants with high antioxidant activity are great of significant in the pharmaceutical and cosmetic industries. Oxidative stress plays a major part in the development of many diseases including cancer, which is known imbalance free radicals and antioxidants. Herein, new natural antioxidant compounds [...] Read more.
Many plants with high antioxidant activity are great of significant in the pharmaceutical and cosmetic industries. Oxidative stress plays a major part in the development of many diseases including cancer, which is known imbalance free radicals and antioxidants. Herein, new natural antioxidant compounds have great interest in the scientific research. The genus Silene is a major group in the Caryophyllaceae family. In Turkey, Silene species have been used for several medicinal purposes such as skin softening, asthma, bronchitis. In our study, the antioxidant capacity of three Silene species (S. conoidea, S. dichotoma and S. italica) were evaluated by different in vitro assays, including free radical scavenging, reducing power, metal chelating, and phosphomolybdenum. In addition, total phenolic and flavonoid contents were analyzed spectrophotometrically. The water extracts contained higher total phenolic content than ethyl acetate extracts. All extracts showed antioxidant capacity. This data indicated that Silene species could potentially be used as antioxidant sources in pharmaceutical and cosmetic areas. Full article
Open AccessAbstract
A New Approach: Treatment with Sodium Vanadate and Cisplatin Combination for Human Hepatocellular Carcinoma
Proceedings 2019, 40(1), 14; https://doi.org/10.3390/proceedings2019040014 - 25 Dec 2019
Viewed by 196
Abstract
The most common primary liver malignancy is hepatocellular carcinoma. Various chemotherapy drugs are used for treatment. These drugs have high toxicity to liver tissue. More effective, less toxic options should be preferred for treatment. The aim of this study is to investigate the [...] Read more.
The most common primary liver malignancy is hepatocellular carcinoma. Various chemotherapy drugs are used for treatment. These drugs have high toxicity to liver tissue. More effective, less toxic options should be preferred for treatment. The aim of this study is to investigate the cytotoxic effect of cisplatin and sodium vanadate combination (NaV) in hepatocellular carcinoma. The hepatocellular cancer cell line (HepG2) was used in this study. Increased concentration of cisplatin and a selected concentration of sodium vanadate were treated to HepG2 cells for 24- and 72-hours incubation times. The proliferation of HepG2 cells decreased with the combination of NaV and cisplatin. While cisplatin was effective in 10–4 M concentration in the proliferation of HepG2 cells, 10–4 M cisplatin with 10–3 M NaV in combination was less effective in the proliferation of HepG2 cells. According to these results, NaV and cisplatin show toxic effects on hepatocellular carcinoma cells. However, the combination of cisplatin and NaV has a less toxic effect than cisplatin and NaV on hepatocellular carcinoma cells. Full article
Open AccessAbstract
Investigation of the Effects of Momordica charantia Extract on Cell Survival and Migration in U87G Glioblastoma Cell Line
Proceedings 2019, 40(1), 18; https://doi.org/10.3390/proceedings2019040018 - 26 Dec 2019
Viewed by 211
Abstract
Glioblastoma multiforme (GBM) is a type of cancer which has the highest mortality rate among brain cancers (1–2). Momordica charantia, known as bitter melon, is a plant its pharmacological activities and nutritional properties. Due to contains bioactive compounds, M. charantia is used for [...] Read more.
Glioblastoma multiforme (GBM) is a type of cancer which has the highest mortality rate among brain cancers (1–2). Momordica charantia, known as bitter melon, is a plant its pharmacological activities and nutritional properties. Due to contains bioactive compounds, M. charantia is used for cancer treatments, inflammation-related diseases and diabetes (3–4). In this study, it was aimed to investigate the effects of M. charantia extract on cell viability, cytotoxicity and migration capacity in U87G cell line. U87G was cultured in DMEM-high glucose containing FBS 10% (v/v) and penisillin-streptomicin 1% (v/v). Cells were incubated at 37 °C in a humidified 5% CO2 incubator. The cytotoxic effect of M.charantia extract was determined by MTT analysis, cell viability by survival analysis and migration by wound-healing analysis. The results were evaluated by using ANOVA and GraphPad Prism7.0 program (GraphPad Software, La Jolla, CA, USA) in three replicates. IC50 value of M. charantia extract was found 750 μg/mL which is statistically significant (* p < 0.05). The extract had an increasing lethal effect at the 16.6% (24 h), 42.6% (48 h), 79.3% (72 h) and 91.6% (96 h). According to the wound-healing analysis, the wound closed at 24 h in the control group and the wound gradually increased depending on time in the extract treated group. According to the results, M. charantia extract has a cytotoxic and a significant anti-proliferative effect on U87G. It might be used as therapeutic agent against to GBM. However, in order to understand the effect of M. charantia in living organisms, in vivo experiments must be determined. Full article
Open AccessAbstract
The Effect of the Combinations of 5-Fluorouracil, Leptin and Leptin Antagonist in Glioblastoma
Proceedings 2019, 40(1), 19; https://doi.org/10.3390/proceedings2019040019 - 26 Dec 2019
Viewed by 213
Abstract
Glioblastoma (GB) is the most aggressive form of brain tumor and resistant to chemotherapy. New therapeutic approaches are needed to improve the efficacy of chemotherapy. It was reported that there may be a relationship between obesity and poor prognosis in GB treatment. However, [...] Read more.
Glioblastoma (GB) is the most aggressive form of brain tumor and resistant to chemotherapy. New therapeutic approaches are needed to improve the efficacy of chemotherapy. It was reported that there may be a relationship between obesity and poor prognosis in GB treatment. However, there is no study investigating the relationship between leptin, leptin receptor and chemotherapy in GB. The aim of this study was to investigate the cytotoxic effects of 5-Fluorouracil (5-FU) in the treatment of GB in the presence of leptin and leptin receptor antagonist SHLA. LN-405, T98G and U373-MG GB cell lines were used for this purpose. The cytotoxic effects of these molecules in both single and combination were determined by MTT. The sensitivities of GB cell lines to 5-FU were found to be different and leptin and SHLA had no cytotoxic effects in GB cells. It was determined that leptin increased 5-FU toxicity by 8–57% depending on 5-FU dose and cell type in all three cell lines in combination groups. A similar effect was detected in combinations of SHLA with 5-FU (6–58%). This is the first study to show that combinations of 5-FU with leptin and SHLA increase the cytotoxicity of 5-fluorouracil in cancer. Full article
Open AccessAbstract
Quercetin’s Effects on Cell Survival of Resistant GBM Cell Line (T98G) after Repetitive Treatment Combined with Temozolomide
Proceedings 2019, 40(1), 28; https://doi.org/10.3390/proceedings2019040028 - 26 Dec 2019
Viewed by 212
Abstract
Glioblastoma multiforme is one of the most common and aggressive brain tumors. It is mortal and progressive disease despite novel therapies. The mechanism of action of temozolomide (TMZ) is the methylation of DNA guanin at position N7 and O6. This situation triggers apoptosis [...] Read more.
Glioblastoma multiforme is one of the most common and aggressive brain tumors. It is mortal and progressive disease despite novel therapies. The mechanism of action of temozolomide (TMZ) is the methylation of DNA guanin at position N7 and O6. This situation triggers apoptosis by interrupting cell cycle on G2-M. O6-methyl-guanin methyl transferase enzyme decrease the anti-carcinogenic effects of TMZ by detaching methyl at position O6, thus lead to resistance for cytotoxic effect of TMZ. Quercetin has anti-carcinogenic effect on different pathways. So the aim of this study is to investigate the effects of repetitive treatment of TMZ and/or quercetin on resistant GBM cell line (T98G) for TMZ. T98G cell line treated with 50 µM TMZ and/or quercetin 25 µM every 24 hours during 72 hours. Real time cell analysis (RTCA-xCelligence) has been performed for cell life variation and flow cytometry analysis for early or late apoptosis. Cell survival rate of T98G reduced, early and late apoptosis induced with repetitive TMZ and quercetin treatment. Quercetin and TMZ reduced cell life rate on T98G after repetitive treatment. Early and late apoptosis rate affected as increased with quercetin. Full article
Open AccessAbstract
Composition Analysis and Anti-Cancer Properties of Two Endemic Phlomis Species (Phlomis cypria Post and Phlomis brevibracteata Turrill) from Cyprus
Proceedings 2019, 40(1), 29; https://doi.org/10.3390/proceedings2019040029 - 26 Dec 2019
Viewed by 216
Abstract
Recently, different herbal compounds have been studied for their curative properties against Hepatocellular Carcinoma (HCC). There are over 100 Phlomis species native to the Mediterranean region, which have pharmacological activities against gastrointestinal system and liver diseases. Phlomis brevibracteata Turrill (PBT) and Phlomis cypria [...] Read more.
Recently, different herbal compounds have been studied for their curative properties against Hepatocellular Carcinoma (HCC). There are over 100 Phlomis species native to the Mediterranean region, which have pharmacological activities against gastrointestinal system and liver diseases. Phlomis brevibracteata Turrill (PBT) and Phlomis cypria Post (PCP) are endemic plants of North-Cyprus belonging to the Lamiaceae family. In this study, chemical composition of the 70% methanol extracts of Phlomis species were analyzed by LC/MS/MS and antiradical activities were evaluated by DPPH and ABTS+● radical scavenging activity tests. Anti-carcinogenic activities on HCC cell lines were investigated using MTT and wound healing assays, intercellular ROS scavenging activities were tested by DCFH-DA assay. Forsytoside B and caffeoylquinic acids were found as the main phenolic compounds which are possibly responsible for antiradical activities of the plant extracts. Significant decrease in cell viability was noticed for both extracts at concentrations over 1000 µg/mL. PBT treatment also resulted in cell motility inhibition. Additionally, both basal and induced oxidative states of all cell lines significantly were decreased by PBT. Since extracts showed cytotoxic, antioxidant and motility inhibitory activities, Phlomis species can be a good candidate for further studies with the goal of new anticancer chemotherapeutic discoveries. Full article
Open AccessAbstract
A Different Approach to Cancer and Drug Resistance in Cancer: Parasites
Proceedings 2019, 40(1), 30; https://doi.org/10.3390/proceedings2019040030 - 26 Dec 2019
Viewed by 237
Abstract
Encephalitozoon intestinalis (E. intestinalis) is a parasite that causes opportunistic infections that can cause death in immune compromised patients. The aim of this study was to determine the effect of parasite on genes involved in host cell apoptosis. The CaCo cells were [...] Read more.
Encephalitozoon intestinalis (E. intestinalis) is a parasite that causes opportunistic infections that can cause death in immune compromised patients. The aim of this study was to determine the effect of parasite on genes involved in host cell apoptosis. The CaCo cells were infected with E. intestinalis 50506 (ATCC) strain. Apoptosis was induced in both control and parasite-infected groups after infection. RNA isolation and cDNA extraction were then performed. Changes in the expression of genes involved in apoptotic pathways were evaluated quantitatively (qPCR) by Real-Time PCR. The obtained data were analyzed by 2-ΔΔCt method. E. intestinalis inhibits the CASP6, DR4, DR5, DCR2 genes that regulate the transcription of the genes known as the death gene of cells in CaCo cells. TP53 regulates the transcription of certain genes involved in cell death. DR4, DR5 and DCR2 are inhibited by the introduction of E. intestinalis into the cell. Caspase 6 is one of the caspases that induces apoptosis. As can be seen from the activation of these genes, E. intestinalis inhibits transcription genes in the pro-apoptotic pathway of the cell. We think that this parasite, which is commonly found in cancer patients, should be investigated for the effect of drug resistance in cancer treatment. This study was supported by Erciyes University. Project ID: TCD-2016-7042. Full article
Open AccessAbstract
Metabolomics Studies on Asteraceae Family Plants to Find Cytotoxic Drug Candidates
Proceedings 2019, 40(1), 36; https://doi.org/10.3390/proceedings2019040036 - 30 Dec 2019
Viewed by 202
Abstract
Cancer is one of the major causes of death globally, which involves uncontrollable growth and spread of abnormal cells. Cytotoxic plant extracts may act on various cancer cells. In this study cytotoxicity of five cultivated Asteraceae plant extracts (Echinacea purpurea L., Achillea filipendulina [...] Read more.
Cancer is one of the major causes of death globally, which involves uncontrollable growth and spread of abnormal cells. Cytotoxic plant extracts may act on various cancer cells. In this study cytotoxicity of five cultivated Asteraceae plant extracts (Echinacea purpurea L., Achillea filipendulina L., Achillea millefolium L., Tanacetum parthenium L., Silybum marianum L.) has been investigated on different cell lines. Metabolomic profiling of the plants was performed using the LC-qTOF-MS system. In vitro MTT assay applied for determine cytotoxic activity of samples on HT29 (Human colon cancer cells) and L929 (mouse fibroblast) cells. Correlation has been examined between cytotoxicity and metabolomic profile to find active seconder metabolites (r ≥ 0.60, r ≤ −0.60). Total 585 seconder metabolites have been detected for five Asteraceae plants. 118 metabolite showed positive correlation with the cell viability on L929 cell lines while 79 metabolites showed negative correlation. 112 metabolites showed positive correlation with cytotoxic activity on HT29 cell lines while 70 metabolites showed negative. 18 uncommon metabolites were detected in S. marianum extract which has selective cytotoxic activity on cell lines. 16 common metabolites were highly correlated positively as selective cytotoxic activity. These results showed us correlation analyzes between activity and metabolomic profile can be an easy and appropriate method to determine active seconder metabolites in plant extracts. Full article
Open AccessAbstract
The Anti-Tumoral Effects of Wolfberry (Lycium barbarum) on Experimentally Induced Ehrlich Ascites Carcinoma in Mice
Proceedings 2019, 40(1), 38; https://doi.org/10.3390/proceedings2019040038 - 30 Dec 2019
Viewed by 184
Abstract
Wolfberry (Lycium barbarum) shows strengthen immune system, antioxidant and anticancerogenic effect. In this research, the effects of Wolfberry's extract fractions, cultivated in Kayseri, investigated on Ehrlich ascites tumor (EAT) using in vivo and in vitro techniques. For in vivo study, 200 [...] Read more.
Wolfberry (Lycium barbarum) shows strengthen immune system, antioxidant and anticancerogenic effect. In this research, the effects of Wolfberry's extract fractions, cultivated in Kayseri, investigated on Ehrlich ascites tumor (EAT) using in vivo and in vitro techniques. For in vivo study, 200 mg/kg fractions of Wolfberry extract (above and below 50 kDa) were injected ip to EAT injected Balb/C mice. EAT cells were also cultured in the presence of Wolfberry's extract fractions (1500, 2000 µg/ml) to examine cell vitality and apoptosis using the Muse Cell Analyzer. Histopathological examination of intra-abdominal organs showed that there were decrease in the EAT cells adherence in the Wolfberry applied tissue groups when compared to the control. According to in vitro results, the both extract fractions (above and below 50 kDa) increased apoptosis in cancer cells. However, total apoptotic cell percentage was higher and statistically significant in groups above 50 kDa (1500, 2000 mg/ml) (p < 0.05). Previous literature and the results of the present study reveal that the consumption of wolfberry—which is also produced in Turkey—might be effective in preventing the formation of cancer and the deceleration of its progress. Full article
Open AccessAbstract
Evaluation of Cytotoxic Effects of Carnosic Acid Alone and Combination with Cisplatin in HepG2 Cells
Proceedings 2019, 40(1), 39; https://doi.org/10.3390/proceedings2019040039 - 31 Dec 2019
Viewed by 173
Abstract
Natural products are important in prevention and treatment of cancer because of their antitumor effect and reducing side effects of chemotherapeutic drugs. The aim of this study was to investigate the potential cytotoxic effecs of carnosic acid and in combination with cisplatin in [...] Read more.
Natural products are important in prevention and treatment of cancer because of their antitumor effect and reducing side effects of chemotherapeutic drugs. The aim of this study was to investigate the potential cytotoxic effecs of carnosic acid and in combination with cisplatin in liver cancer cells. Cytotoxicity was assessed using MTT assay for 24/48 hours. The intracellular ROS levels were determined using the oxidation‐sensitive fluorescent probes DCFH‐DA. Changes in the mitochondrial membrane potential (MMP) were detected using JC-1 commercial kit. Concentrations were selected for carnosic acid and cisplatin according to IC50 values. As a results, % cell viability decreased with concentration/time dependent and combination treatments showed potentiated effect at 48 hours exposure. According to DCFH-DA assay, it was observed that carnosic acid and combinations with cisplatin reduced intracellular ROS levels in presence of H2O2. Carnosic acid and its combinations reduced MMP. Our results showed that carnosic acid has the potential to inhibit growth in HepG2 cells without increasing ROS production. In conclusion, carnosic acid alone and combination with cisplatin may be promising for the prevention and treatment of liver cancer. Full article
Open AccessAbstract
Some Wild Edible Mushroom Anticancer Activity Against Prostate Cell Lines
Proceedings 2019, 40(1), 40; https://doi.org/10.3390/proceedings2019040040 - 31 Dec 2019
Viewed by 189
Abstract
Prostate cancer is one of the cause of mortality and morbidity in men. High nutritional quality mushrooms have been consumed as food for a long time and Thanks to their bioactive components, they can be used in many fields such as pharmaceuticals, cosmetic [...] Read more.
Prostate cancer is one of the cause of mortality and morbidity in men. High nutritional quality mushrooms have been consumed as food for a long time and Thanks to their bioactive components, they can be used in many fields such as pharmaceuticals, cosmetic products, dietary supplements and functional food production. The purpose of the research was to evaluate these derivatives against in vitro to obtain novel specific and effective anticancer agents against prostate cancer. In the study, Amanita caesarea, Sparassis crispa, Lepista nuda, Auricularia auricula, Tricholoma terreum and Lentinus tigrinus fungi were used. Anticancer activities of the compounds were evaluated in vitro by using MTT method against PC-3 and DU-143 (androgen-independent human prostate cancer cell lines) prostate cancer cell lines. Cisplatin was used as the positive sensitivity reference standard. The most effective among these fungus species biological activity against PC3 cancer cell line (IC50 = 327.34 µM), against DU-145 (IC50 = 459.19 µM). Full article

Poster Presentations

Open AccessAbstract
Investigation of Antiinflamatory Effects of Origanum majorana L. Extract in LPS-Induced Beas-2b and A549 Cells
Proceedings 2019, 40(1), 8; https://doi.org/10.3390/proceedings2019040008 - 25 Dec 2019
Viewed by 191
Abstract
Origanum majorana (OM) L. belongs to Lamiaceae family and has antiinflammatory effects. The common feature of the causes of lung cancer is the coexistence of inflammatory events. The aim of this study was to investigate the anti-inflammatory activity of OM in non-small cell [...] Read more.
Origanum majorana (OM) L. belongs to Lamiaceae family and has antiinflammatory effects. The common feature of the causes of lung cancer is the coexistence of inflammatory events. The aim of this study was to investigate the anti-inflammatory activity of OM in non-small cell lung cancer (A549) and human bronchial epithelial cell line (Beas-2b). The effects of OM extract were investigated by using MTT analysis and xCELLigence real-time cell analysis. The major compounds were identified by high pressure liquid chromatography with diode array detection coupled with electrospray ion trap mass spectrometry (LC-DAD-ESI-MS). In this study, LPS was administered to A549 and Beas-2b cells and inflammatory responses were triggered. Antiinflammatory activity of OM extract was evaluated by Western blot method COX-2 expression in both cell lines with LPS induced inflammation. OM cytotoxic activity in the Beas-2b cells triggered inflammation by both alone and with LPS, whereas cytotoxicity in the A549 cells showed at high concentrations. It was concluded that OM increased the expression of COX-2 in its use alone, but it showed antioxidative effect by suppressing COX-2 as a concentration dependent inhibition in cases where inflammation was triggered by LPS. On the basis of the composition of these active extracts it is apparent that flavonoids, i.e. apigenin, luteolin, and their glycoside derivatives, along with phenolic acids, i.e. rosmarinic acid and salvianolic acids, are the major principles of the OM extract. It was concluded that it seems to be promising to investigate the anticancer activity of this compound which has antiinflammatory activity. Full article
Open AccessAbstract
Autocrine Growth Hormone (GH)-Mediated Triptolide Resistance Overcame by Metformin Co-Treatment in MDA-MB231 Breast Cancer Cells Through ER Stress Pathway
Proceedings 2019, 40(1), 9; https://doi.org/10.3390/proceedings2019040009 - 25 Dec 2019
Viewed by 222
Abstract
Breast cancer is the most common cancer in women worldwide and the second most common cancer overall. Autocrine growth hormone (GH) expression induced cell proliferation, growth, invasion-metastasis in vitro and in vivo breast cancer models. Moreover, forced GH signaling acts as a drug [...] Read more.
Breast cancer is the most common cancer in women worldwide and the second most common cancer overall. Autocrine growth hormone (GH) expression induced cell proliferation, growth, invasion-metastasis in vitro and in vivo breast cancer models. Moreover, forced GH signaling acts as a drug resistance profile in breast cancer cell lines against chemotherapeutic drugs such as tamoxifen, mitomycin C, doxorubicin and curcumin. Triptolide, an active plant extract from Tripterygium wilfordii, has been shown to induce apoptotic cell death in various cancer cells such a prostate, colon, breast cancer. Metformin, a common therapeutic agent for type II Diabetes mellitus, has been shown to induce autophagy, endoplasmic reticulum (ER) stress and apoptotic cell death in cancer cells. Our aim is to demonstrate the potential effect of metformin on triptolide-mediated drug resistance in autocrine GH expressing MDA-MB-231 breast cancer cells through Endoplasmic reticulum (ER) stress. Autocrine GH-mediated triptolide (20 nM) resistance overcame by metformin (2 mM) co-teatment in MDA-MB231 breast cancer cells through accelerating cell viability loss, growth inhibition compared to alone triptolide treatment. Combined treatment increased apoptotic cell death via CHOP activation, IRE1α upregulation. Consequently, we suggest that triptolide can be more effective with metformin combination in MDA-MB-231 GH+ drug resistant breast cancer cells. Full article
Open AccessAbstract
Epibrassinolide Promotes the Apoptotic Potential of Gemcitabine in Pancreatic Cancer Cells
Proceedings 2019, 40(1), 10; https://doi.org/10.3390/proceedings2019040010 - 25 Dec 2019
Viewed by 186
Abstract
Pancreatic cancer is a lethal disease for which the incidence and mortality rates are close. Patients with advanced stage have median survival of three months. Gemcitabine (GEM), the anticancer analog of deoxycytidine, has been considered standard care of pancreatic cancer. However, disease progression [...] Read more.
Pancreatic cancer is a lethal disease for which the incidence and mortality rates are close. Patients with advanced stage have median survival of three months. Gemcitabine (GEM), the anticancer analog of deoxycytidine, has been considered standard care of pancreatic cancer. However, disease progression usually occurs. Despite the effort for better treatment options, phase trials fail due to severe side effects. Epibrassinolid (EBR) is a member of brassinnosteroids with similar chemical structure to steroid hormones. Our group showed that EBR induces apoptosis via endoplasmic reticulum stress induction both in in vitro and in vivo cancer models, without effecting non-cancerous cells or non-tumor bearing mouse. Our aim in this study is to evaluate whether EBR has the potential to increase the apoptotic effect of GEM in AsPc1 pancreatic cells. We showed by MTT assay that EBR has apoptotic efficiency in AsPc1 cells and it also increases the cell viability loss when combined with GEM. The combination of EBR (30 µM) and GEM (100 µM) further increases mitochondrial membrane potential loss and nuclear condensation. In addition, exposure of cells to EBR and GEM co-treatment induces subG1 apoptotic population showed by FACS flow analysis. Consequently, we suggest that the effect of GEM can be increased with EBR combination. Full article
Open AccessExtended Abstract
Microwave-Assisted and Green Fabrication of Carbon Quantum Dots from Viburnum opulus for Potential Bioimaging Applications
Proceedings 2019, 40(1), 11; https://doi.org/10.3390/proceedings2019040011 - 25 Dec 2019
Viewed by 174
Abstract
Early diagnosis is very strategic for today’s diseases such as cancer and infectious diseases. [...] Full article
Open AccessAbstract
Triptolide Resistance Was Prevented by Metformin Co-Treatment Under Increased Growth Hormone Signaling Conditions in MDA-MB-231 Cells
Proceedings 2019, 40(1), 12; https://doi.org/10.3390/proceedings2019040012 - 25 Dec 2019
Viewed by 184
Abstract
Breast cancer is identified as the most common cancer among women and the leading cause of cancer-related deaths. Increased expression of growth hormone (GH) has been found to cause cell growth, drug resistance and invasion-metastasis in breast cancer. Triptolide is a diterpenoid isolated [...] Read more.
Breast cancer is identified as the most common cancer among women and the leading cause of cancer-related deaths. Increased expression of growth hormone (GH) has been found to cause cell growth, drug resistance and invasion-metastasis in breast cancer. Triptolide is a diterpenoid isolated from Tripterygium wilfordii with anti-cancer activity. Our data showed that GH overexpressing MDA-MB-231 cells exhibited a resistance mechanism against tripitolide treatment when compared to wild type MDA-MB-231 cells. To overcome the resistance, we combined triptolide with metformin, an anti-diabetic agent with anti-tumorigenic effect and a potential adjuvant in the management of breast cancer. Our findings indicated that GH+ cells exhibited increased cell viability loss, mitochondrial membrane potential loss and apoptotic cell death with metformin co-treatment. In addition, colony sizes were significantly decreased due to combined treatment. Autophagy is a process of cellular self-degradation during which macromolecules, damaged organelles are delivered to the lysosome in order to control energy level under stressed conditions. Cells can control proliferation or apoptosis by changing the level of autophagy, it has been proposed as a chemoresistance mechanism. Our data showed that there was no significant change in the autophagy induction in MDA-MB-231 wt and GH+ cells treated with triptolide and metformin. Full article
Open AccessAbstract
Triptolide-Mediated Apoptotic Cell Death Accelerated by Metformin Co-Treatment in MiaPaca-2 Cells
Proceedings 2019, 40(1), 13; https://doi.org/10.3390/proceedings2019040013 - 25 Dec 2019
Viewed by 200
Abstract
Pancreatic cancer is the fourth most common cause of cancer death worldwide with limited therapeutic potential and low survival rate. A natural agent; triptolide (diterpenoid triepoxide), induce cell viability loss, growth inhibition and apoptotic cell death in various cancer cells such as breast, [...] Read more.
Pancreatic cancer is the fourth most common cause of cancer death worldwide with limited therapeutic potential and low survival rate. A natural agent; triptolide (diterpenoid triepoxide), induce cell viability loss, growth inhibition and apoptotic cell death in various cancer cells such as breast, prostate and pancreatic cancer. Metformin, a common therapeutic agent for type II Diabetes mellitus, has been shown to induce apoptotic cell death in pancreatic cancer via modulating various pathways such as PI3K/Akt pathways. In this study, our aim was to investigate the potential additional effect of metformin on triptolide-induced apoptotic cell death in MiaPaCa-2 cells. Drugs-mediated cell viability loss, growth inhibition and colony formation potential were examined by MTT, trypan blue exclusion, colony formation, hanging drop assays. Drugs triggered apoptotic cell death was determined by PI FACS flow analysis. According to MTT cell viability assay, 20 nM triptolide decreased cell viability by 78%, but triptolide and metformin co-treatment decreased cell viability by 57%. Metformin co-treatment increased the triptolide-mediated cell growth inhibition, and prevention of colony formation in MiaPaCa-2 cells. In addition, co-treatment increased triptolide-triggered mitochondrial membrane potential loss, cell death and ROS generation. In conclusion, metformin co-treatment accelerated triptolide-triggered apoptotic cell death in MiaPaCa-2 cells. Full article
Open AccessAbstract
The Effect of Schisandrin B on the Development of Multiple Sclerosis
Proceedings 2019, 40(1), 15; https://doi.org/10.3390/proceedings2019040015 - 25 Dec 2019
Viewed by 189
Abstract
Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating neurodegenerative disease targeting the central nervous system. The pathogenesis of MS is a process of innate and adaptive immune system components. In particular, Th17 and Treg balance play an important role in the pathogenesis of [...] Read more.
Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating neurodegenerative disease targeting the central nervous system. The pathogenesis of MS is a process of innate and adaptive immune system components. In particular, Th17 and Treg balance play an important role in the pathogenesis of MS. Several studies have shown that Th17 cells play a critical role in the pathogenesis. Schisandrin B (Sch B) is one of the most abundant and active dibenzocyclooctadiene derivatives found in the fruit of Schisandra chinensis. The aim of this study was to investigate the therapeutic effect of Sch-B and its effect on the immune cell priming in a mouse model of experimental autoimmune encephalomyelitis (EAE). Mice were immunized with MOG35–55 peptide. From day 0, the control group received DMSO, and the Sch-B group received DMSO + Sch-B (60 mg/kg) with intraperitoneal injection every other day. On the 7th day, all mice were sacrificed and the draining lymph nodes and spleens were removed. The Foxp3 expression, Stat3 phosphorylation and the cytokines of IL-17A, IFN-γ, GM-CSF, IL-6, IL-10 and IL-22 produced from lymphocytes were analyzed by flow cytometry. In the T lymphocytes from lymph node analyzed, IL-6 and IL-17 decreased, while IL-22 and IL-10 cytokines and Foxp3 expression increased. In the spleen T lymphocytes analyzed, Stat3 phosphorylation decreased and IL-17 cytokine increased, while IL-10 and IL-22 cytokines and Foxp3 expression increased. These results show that Sch-B decreased Th17 and increased Treg cells at the onset of EAE. In addition, EAE was scored for 18 days, Sch-B decreased the EAE clinical scores compared to the control. These results show a therapeutic effect of Sch-B in murine MS model, and warrant further studies. Full article
Open AccessAbstract
The Effect of Alantolactone on the Development of Multiple Sclerosis
Proceedings 2019, 40(1), 16; https://doi.org/10.3390/proceedings2019040016 - 25 Dec 2019
Viewed by 221
Abstract
Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating neurodegenerative disease targeting the central nervous system. The pathogenesis of MS is an immune mediated process involving innate and adaptive immune system components. In particular, Th17 and Treg balance play an important role in the [...] Read more.
Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating neurodegenerative disease targeting the central nervous system. The pathogenesis of MS is an immune mediated process involving innate and adaptive immune system components. In particular, Th17 and Treg balance play an important role in the pathogenesis of MS. Several studies have shown that Th17 cells play a critical role in the pathogenesis. Alantolactone (ALT) is a sesquiterpene lactone produced by Inula helenium. The aim of this study was to investigate the therapeutic effect of ALT and its effect on the immune cell priming in a mouse model of experimental autoimmune encephalomyelitis (EAE). Mice were immunized with MOG35–55 peptide. From day 0, the control group received DMSO, and the ALT group received intraperitoneal DMSO + ALT (10 mg/kg) every other day. On the 7th day, all mice were sacrificed and draining lymph nodes and spleens were removed. The Foxp3 expression, Stat3 phosphorylation and the cytokines of IL-17A, IFN-γ, GM-CSF, IL-6, IL-10 and IL-22 produced from lymphocytes were analyzed by flow cytometry. When the T lymphocytes obtained from lymph node analyzed, IL-6, IL-17 partial and IL-22, IL-10 cytokines and Foxp3 expression increased. When the spleen T lymphocytes analyzed, Stat3 phosphorylation and IL-17 cytokine decreased, while IL-10, IL-22 cytokines and Foxp3 expression increased. These results show that ALT increased Treg cells at the onset of EAE. In addition, EAE was scored for 18 days, ALT decreased the EAE scores compared to the control. These results show a therapeutic effect of ALT in murine MS model, and warrant further studies. Full article
Open AccessAbstract
Focusing on the Chemical Characterization, Antioxidant and Cytotoxic Properties of Two Geophytes: Crocus Pallasii and Cyclamen Cilicium
Proceedings 2019, 40(1), 17; https://doi.org/10.3390/proceedings2019040017 - 25 Dec 2019
Viewed by 213
Abstract
Species of the Crocus and Cyclamen genus have been reported to possess diverse biological properties. In the current work, the antioxidant and cytotoxic effects of the methanolic extracts of C. pallasii and C. cilicium aerial and underground parts were evaluated. The flower extracts [...] Read more.
Species of the Crocus and Cyclamen genus have been reported to possess diverse biological properties. In the current work, the antioxidant and cytotoxic effects of the methanolic extracts of C. pallasii and C. cilicium aerial and underground parts were evaluated. The flower extracts of C. pallasii and C. cilicium possessed highest flavonoid content. Highest phenolic content was recorded from C. cilicium root extract (47.62 mg gallic acid equivalent/g extract). C. cilicium root extract showed significantly (p < 0.05) high radical scavenging (94.28 and 139.60 mg trolox equivalent [TE]/g extract, against DPPH and ABTS radicals, respectively) and reducing potential (173.30 and 109.53 mg TE/g extract, against CUPRAC and FRAP, respectively). Methanolic extracts of C. pallasii and C. cilicium showed toxicity against breast cancer cell lines. In the light of the above findings, C. cilicium might be considered as an interesting candidate in the development of anti-cancer agent, possessing antioxidant properties. Full article
Open AccessAbstract
Antioxidant Effects of Different Extracts from Root and Aerial Parts of Scorzonera hieraciifolia
Proceedings 2019, 40(1), 20; https://doi.org/10.3390/proceedings2019040020 - 26 Dec 2019
Viewed by 230
Abstract
The genus Scorzonera has great potential as traditional drugs and foods in several traditional systems including Turkey. In this current work, we investigated antioxidant properties of different extracts from S. hieraciifolia aerial parts and roots. We used different extracts (dichloromethane, ethyl acetate, hexan, [...] Read more.
The genus Scorzonera has great potential as traditional drugs and foods in several traditional systems including Turkey. In this current work, we investigated antioxidant properties of different extracts from S. hieraciifolia aerial parts and roots. We used different extracts (dichloromethane, ethyl acetate, hexan, methanol and water). To obtain full picture for antioxidant properties, different methods including radical scavenging (DPPH and ABTS), reducing power (CUPRAC and FRAP), metal chelating and phosphomolybdenum assay. Total phenolic and flavonoid contents were also calculated for each extract. Antioxidant abilities and total bioactive components depended on the solvents used. The highest level of phenolic was determined in methanol extracts, followed by water, ethyl acetate, hexan and ethyl acetate. Similar to phenolic contents, the best antioxidant properties were obtained by methanol and water extracts. Based on our findings. S. hieraciifolia extracts could be valuable source to combat oxidative stress related diseases such as cancer. Full article
Open AccessAbstract
In vitro Antioxidant Properties of Bersama abyssinica Stem Bark Extracts
Proceedings 2019, 40(1), 21; https://doi.org/10.3390/proceedings2019040021 - 26 Dec 2019
Viewed by 223
Abstract
Bersama abyssinica, belonging to the Melianthaceae family, is distributed across Sub Saharan Africa. Decoctions of the bark, leaves, and roots of B. abyssinica have been extensively used in traditional medicine to manage many stomach complications such as colic, diarrhea, dysentery, and intestinal [...] Read more.
Bersama abyssinica, belonging to the Melianthaceae family, is distributed across Sub Saharan Africa. Decoctions of the bark, leaves, and roots of B. abyssinica have been extensively used in traditional medicine to manage many stomach complications such as colic, diarrhea, dysentery, and intestinal worms. In this study, we examined three extracts (ethyl acetate, methanol and water) obtained from B. abyssinica stem barks in terms of antioxidant properties. The antioxidant abilities were investigated by different chemical methods, including free radical scavenging (DPPH and ABTS), reducing power (CUPRAC and FRAP), metal chelating and phosphomolybdenum assay. In addition, total phenolic and flavonoid contents in the extracts were calculated. The highest level of phenolics was determined in water extract (230.83 mg GAE/g extract), followed by methanol (216.79 mg GAE/g extract) and ethyl acetate (100.57 mg GAE/g extract). In same line with total phenolic content, the best antioxidant properties were noted for water and methanol extracts. Our findings suggested that B. abyssinica stem bark extracts could be considered as promising sources of natural antioxidants. Full article
Open AccessAbstract
The Effect of Trichostatin A on Radiosensitivity in Glioblastoma
Proceedings 2019, 40(1), 22; https://doi.org/10.3390/proceedings2019040022 - 26 Dec 2019
Viewed by 271
Abstract
Glioblastoma (GB) is the most lethal brain tumor that resists standard treatments because of its high malignancy. Radiotherapy (RT) directly affects the clinical success on GB treatment. Epigenetic modifications occur in GB cells at a high rate. Improving the therapeutic efficacy of RT [...] Read more.
Glioblastoma (GB) is the most lethal brain tumor that resists standard treatments because of its high malignancy. Radiotherapy (RT) directly affects the clinical success on GB treatment. Epigenetic modifications occur in GB cells at a high rate. Improving the therapeutic efficacy of RT over epigenetic modulators may contribute to the development of a targeted treatment in GB. Trichostatin A (TSA), a histone deacetylase inhibitor, a natural antifungal compound. The aim of this study was to investigate the effect of TSA on radiosensitivity when combined with RT in GB cells. Different concentrations of TSA (in the range of 100–1000 nm) and 8 Gy RT were applied to GB LN-405 cells as alone and combination simultaneously. Cell viability was determined by MTT. In the RT application, 3D conformal technique, which can represent GB clinical practice, was used. Cell viability was significantly reduced in both TSA and TSA + RT combination groups compared to control group (p < 0.05). When the TSA was compared with the TSA + RT combination, it was found that TSA increased the radiosensitivity by 17–41% depending on the dose. This is the first study to show that TSA increases the radiosensitivity in GB LN-405 cells in the literature. Full article
Open AccessAbstract
A study on Antioxidant Properties of Different Extracts from Kitaibelia balansae
Proceedings 2019, 40(1), 23; https://doi.org/10.3390/proceedings2019040023 - 26 Dec 2019
Viewed by 248
Abstract
Nowadays, knowledge of ancient botanical medicinal practices and application of modern phytochemical techniques have provided the excellent tools for the purification and structural elucidation of various phyto-compounds, which, in turn, has given insights into their mode of action on the human body. This [...] Read more.
Nowadays, knowledge of ancient botanical medicinal practices and application of modern phytochemical techniques have provided the excellent tools for the purification and structural elucidation of various phyto-compounds, which, in turn, has given insights into their mode of action on the human body. This study has been designed to investigate for the first time the antioxidant effects of the ethyl acetate, methanolic, and water extracts of Kitaibelia balansae. Different chemical methods were performed and the observed abilities depend on the solvent used. The best antioxidant ability was noted in water extract, followed by methanol and ethyl acetate extracts. The highest level of phenolic was also detected in water extract. The present findings suggest that K. balansae can be considered as a potential source of bioactive compounds for novel phytopharmaceuticals development Full article
Open AccessAbstract
GC-MS Analysis and Antioxidant Potential of Essential Oil from Endemic Sideritis rubriflora Hub.-Mor.
Proceedings 2019, 40(1), 24; https://doi.org/10.3390/proceedings2019040024 - 26 Dec 2019
Viewed by 201
Abstract
The genus Sideritis, belonging to the Labiateae family, is represented by more than 150 species distributed mainly in the Mediterranean regions. Member of the genus have been used as beverages, flavorings, and medication. We aimed to shed light on the antioxidant potential [...] Read more.
The genus Sideritis, belonging to the Labiateae family, is represented by more than 150 species distributed mainly in the Mediterranean regions. Member of the genus have been used as beverages, flavorings, and medication. We aimed to shed light on the antioxidant potential of the essential oil of Sideritis rubriflora Hub.-Mor. In this study, antioxidant capacity (DPPH and ABTS radical scavenging, CUPRAC and FRAP, phosphomolibdenum assay, and metal chelating activity) of essential oil of S. rubriflora was investigated with colorimetric methods. Also, essential oil composition of the plant was determined by gas chromatography/mass spectrophotometry (GC-MS). 48 components, representing 95.4% of essential oil of S. rubriflora were identified. β-pinene (10.7%) and Germacrene D (10.7%) were the main constituents of the essential oil. Generally, essential oil of S. rubriflora has shown moderate free radical, reducing power, metal chelating. The reported results supported that the possible use of essential oil of S. rubriflora is a source of natural agents for phytopharmaceutical applications. Full article
Open AccessAbstract
The Effects on Proliferation of siRNA-Mediated GLS1 Inhibition in MDA-MB 231 Breast Cancer Cells
Proceedings 2019, 40(1), 25; https://doi.org/10.3390/proceedings2019040025 - 26 Dec 2019
Viewed by 205
Abstract
The main energy source of cancer cells is known as glucose. However, they use glutamine as a second energy source besides glucose. In this study we investigated effect of siRNA mediated inhibition of glutaminase (GLS1) enzyme in the first step of glutamine metabolism [...] Read more.
The main energy source of cancer cells is known as glucose. However, they use glutamine as a second energy source besides glucose. In this study we investigated effect of siRNA mediated inhibition of glutaminase (GLS1) enzyme in the first step of glutamine metabolism on proliferation and apoptosis which are the main features of cancer. In our study we determined the cell viability by MTS analysis and the apoptosis rate by Annexin V using triple negative MDA-MB 231 cell line belonging to aggressive subtype of breast cancer. Our study demonstrated that siRNA-mediated silencing GLS1 reduced proliferation in this cancer cell line. It has been shown that inhibition of GLS1 significantly decreased cells, but there was no change in the rate of apoptosis. The cause of this decrease may be through a different pathway other than apoptosis. In this study we have shown that GLS1 inhibition does not induce apoptosis in this cell line, contrary to the literature, and activates the death pathway through a different pathway. We believe that interrupting the glutamine energy pathway for cancer cells will be promising approach for cancer treatment and further studies are needed for this. Full article
Open AccessAbstract
The Effect of Cumin on HL60 Cell Line
Proceedings 2019, 40(1), 26; https://doi.org/10.3390/proceedings2019040026 - 26 Dec 2019
Viewed by 225
Abstract
Cancer is one of the most debilitating and traumatic diseases of modern life, for which no curative approach is presently available. Even though the recent therapies used to treat patients with various types of cancer have not been completely effective, adjuvant therapies, including [...] Read more.
Cancer is one of the most debilitating and traumatic diseases of modern life, for which no curative approach is presently available. Even though the recent therapies used to treat patients with various types of cancer have not been completely effective, adjuvant therapies, including the use of medicinal plants, may have some effect in achieving cancer treatment goals. Cumin has also been widely used in traditional medicine to treat a variety of diseases, including hypolipidemia, cancer, and diabetes. We used cumin in different concentrations to observe effect of cumin on HL60 cell line. We used MTT cell viability test to investigate cytotoxic effect of cumin. We made experiment for 24, 48 and 72 h and we incubate our cumin exposed drug 37 °C in CO2 incubator. According to MTT results we found IC50 values for cumin 8.5 mg/mL for 72 h incubation. Generally, cancer cells show drug resistant to especially chemical drugs. Use of plant derived substances may reduce drug resistant on cancer cells. Especially if we use cumin combine with chemical drug, probably we will observe more toxic effect on cancer cell. Because combination effect will reduce drug resistant. Full article
Open AccessAbstract
Comparatively Investigation of Antitumor Activities of Resveratrol and Paclitaxel through Apoptosis and Autophagy in A549 Cells
Proceedings 2019, 40(1), 27; https://doi.org/10.3390/proceedings2019040027 - 26 Dec 2019
Viewed by 228
Abstract
Resveratrol, a natural product, has many biological effects including antitumor effects. Paclitaxel, a chemotherapeutic drug, has been widely used in the treatment of lung cancer. Although the antitumor effects of resveratrol and paclitaxel in A549 cells have been studied in separately before, in [...] Read more.
Resveratrol, a natural product, has many biological effects including antitumor effects. Paclitaxel, a chemotherapeutic drug, has been widely used in the treatment of lung cancer. Although the antitumor effects of resveratrol and paclitaxel in A549 cells have been studied in separately before, in this study comparatively investigation the anticancer effects of resveratrol and paclitaxel on the apoptosis and autophagy in A549 cells is aimed. The effects on A549 cell viability of resveratrol and paclitaxel (Taxol) were determined by MTT assay. mRNA transcription levels of Bax, Bcl-2 and caspase-3 and protein expression levels of Bax, Bcl-2 and LC3-II were determined by RT-qPCR and western blot analysis, respectively. Our results demonstrated that resveratrol and paclitaxel inhibited the viability of A549 cells. RT-qPCR and western blot analysis showed that paclitaxel stimulated apoptotic cell death in A549 cells by more increasing pro-apoptotic Bax and caspase-3 levels and by more decreasing anti-apoptotic Bcl-2 level in comparison with resveratrol. On the other hand, resveratrol stimulated autophagic cell death by more increasing the level of an autophagic marker LC3-II compared to paclitaxel. In conclusion, we showed that resveratrol exerts its antitumor effects through the induction of autophagy in A549 cells compared to paclitaxel. However, it should be investigated the synergistic effects of resveratrol in combination with paclitaxel on A549 cells. Thus, resveratrol may enhance the effect of paclitaxel on apoptosis by inducing autophagy in A549 cells. Full article
Open AccessAbstract
Anti-carcinogenic Activities of Different Extracts of Arum rupicola Boiss. var. rupicola from Turkey
Proceedings 2019, 40(1), 31; https://doi.org/10.3390/proceedings2019040031 - 26 Dec 2019
Viewed by 167
Abstract
The Arum L. in the Araceae family belongs to flowering plants. It is represented by 14 species and four varieties. In total, there are 18 taxa in Turkey. Arum rupicola Boiss. var. rupicola is one of taxa among them. Traditionally, boiled and dried [...] Read more.
The Arum L. in the Araceae family belongs to flowering plants. It is represented by 14 species and four varieties. In total, there are 18 taxa in Turkey. Arum rupicola Boiss. var. rupicola is one of taxa among them. Traditionally, boiled and dried leaves are used as food supplement in folk medicine in Turkey. In our previous study, the results showed that different extracts of tubers have varying levels of anticholinesterase activity. In this study, anti-carcinogenic activities were evaluated of the hexane, ethyl acetate, 70% methanol and distilled water extracts of A. rupicolaa var. rupicola on SK-HEP-1 adenocarcinoma cell line. MTT and wound healing assays were used to assess cytotoxicity and 2D cell motility, respectively. Results showed that distilled water extract has the maximum potency and consistent cytotoxic and anti-motility effects on SK-HEP-1 cells. Full article
Open AccessAbstract
Cytotoxic Activities of Different Extracts of Teucrium divaricatum Kotschy ssp. canescens (Celak.) from Cyprus
Proceedings 2019, 40(1), 33; https://doi.org/10.3390/proceedings2019040033 - 26 Dec 2019
Viewed by 191
Abstract
The genus Teucrium belonging to the Lamiaceae family, grows in the Eastern Mediterranean region from Turkey to Palestine. Teucrium divaricatum Kotschy ssp. canescens (Celak.) is an endemic plant in North Cyprus. Herbal parts of Teucrium is used as an infusion for stomachic purposes [...] Read more.
The genus Teucrium belonging to the Lamiaceae family, grows in the Eastern Mediterranean region from Turkey to Palestine. Teucrium divaricatum Kotschy ssp. canescens (Celak.) is an endemic plant in North Cyprus. Herbal parts of Teucrium is used as an infusion for stomachic purposes as traditional medicine in Cyprus. Infusion of this plant is used orally in case of fever and common cold, also in association with inhalation of the steam. Externally, the infusion of the plant is also used in wound healing. In this study, the 70% methonolic extract of T. divaricatum ssp. canescens herba was fractionated by using ethyl acetate (TDE) and buthanol (TDB). TDE and TDB extracts of herbal parts of the plant were used in different concentrations to assess the anti-carcinogenic activity on liver adenocarcinoma cell line SK-HEP-1 using MTT assay. Results showed that both fractions have cytotoxic effects on SK-HEP-1 cells with different levels. Full article
Open AccessAbstract
Cytotoxic Effects of Phlomis Brevibracteata Turril. on SK-HEP-1 Adenocarcinoma Cell Line
Proceedings 2019, 40(1), 34; https://doi.org/10.3390/proceedings2019040034 - 27 Dec 2019
Viewed by 204
Abstract
Phlomis is a large genus in the Lamiaceae family with over 100 species distributed throughout Europe, Asia and North Africa. Some species of Phlomis are used in folk medicine as a stimulant, tonic, and for wound healing. Many studies have shown that different [...] Read more.
Phlomis is a large genus in the Lamiaceae family with over 100 species distributed throughout Europe, Asia and North Africa. Some species of Phlomis are used in folk medicine as a stimulant, tonic, and for wound healing. Many studies have shown that different Phlomis species have anti‐inflammatory, immunosuppressive, free radical scavenging, antimicrobial, anti-ulcerogenic and anti-mutagenic activities. Among these species, Phlomis brevibracteata, Turrill, is an endemic plant which grows in Kyrenia, Karpasia, Nicosia and Limassol regions of Cyprus. In our previous studies, we found that methanol extract (PBM) has anti-carcinogenic activity, in terms of cytotoxicity and 2D motility inhibition. In this study, we tried to find out potential anti-carcinogenic activity of hexane (PBH), ethyl acetate (PBE) and butanol (PBB) sub-crude extracts of the methanol-extracts of the same plant. PBH, PBE and PBB extracts of herbal parts of the plant were used in different concentrations to assess the anti-carcinogenic activity on liver adenocarcinoma cell SK-HEP-1. MTT and wound healing assays were carried out to determine anti-cancinogenic activities. Our findings showed that all three extracts have negative effects on cell viability and motility with different levels. Among these extracts, PBE and PBH extracts were more potent than PBB in terms of IC50 values. Full article
Open AccessAbstract
Cisplatin and Paclitaxel Modulated the Cell Survival Potential of Prostate Cancer Cells
Proceedings 2019, 40(1), 42; https://doi.org/10.3390/proceedings2019040042 - 05 Jan 2020
Viewed by 196
Abstract
Prostate cancer is the second common cause of death among men worldwide. In the treatment of prostate cancer, conventional chemotherapeutics are commonly used. The plant alkaloid Paclitaxel and platinum-based cisplatin are the most common chemotherapy drugs. The transcription factor p53 has a potential [...] Read more.
Prostate cancer is the second common cause of death among men worldwide. In the treatment of prostate cancer, conventional chemotherapeutics are commonly used. The plant alkaloid Paclitaxel and platinum-based cisplatin are the most common chemotherapy drugs. The transcription factor p53 has a potential target in the regulation of cell response to DNA damage of prostate cancer. Although the effectiveness of these drugs on prostate cancer cell progression had been proved, the mechanistic action of these drugs on the progression of the disease is not detailed explained. In this study, we aim to examine the function of p53 overexpression in prostate cancer cell survival. Therefore, we treated wild type (wt) and p53 overexpressed PC3 (p53+) prostate cancer cells with cisplatin or paclitaxel. According to the MTT Cell Viability assay, cisplatin (12.5–25–50 µM) was found to be more effective decreasing PC3 and PC3 p53+ cell viability in a dose-dependent manner compared to paclitaxel (12.5–25–50 nM). Colony formation assay showed that treatment of cells with cisplatin or paclitaxel caused the loss of colony forming ability of PC3 and PC3 p53+ cells. In addition, the critical apoptotic markers Caspase-3 and Caspase-9 expressions were altered with cisplatin or paclitaxel treated PC3 wt and p53+ cells. Full article
Open AccessAbstract
Turkish Endemic Achillea Species Protect Human Neuroblastoma SH-SY5Y Cells Against Hydrogen Peroxide-Induced Cytotoxicity
Proceedings 2019, 40(1), 43; https://doi.org/10.3390/proceedings2019040043 - 09 Jan 2020
Viewed by 215
Abstract
The genus Achillea L. belongs to Asteraceae (Compositae), the largest family of vascular plants. There are 50 species, which of 24 is endemic in this genus in Turkey. Achillae species are used as a tonic, anti-inflammatory, anti-spasmodic, diaphoretic, diuretic and emmenagogic agents and [...] Read more.
The genus Achillea L. belongs to Asteraceae (Compositae), the largest family of vascular plants. There are 50 species, which of 24 is endemic in this genus in Turkey. Achillae species are used as a tonic, anti-inflammatory, anti-spasmodic, diaphoretic, diuretic and emmenagogic agents and have been used for treatment of hemorrhage, pneumonia, rheumatic pain and wounds healing traditionally. The imbalanced antioxidant systems leads to various pathophysiological conditions such as inflammation, neurodegenerative diseases and cancer. Achillea species have several components; essential oils, sesquiterpenes and phenolic compounds such as flavonoids and phenolic acids. Phenolic compounds and flavonoids are the most important medicinal metabolites of Achillea species. Flavonoids have been reported to exert a wide range of biological activities including anti-inflammatory, antioxidant and anti-tumor effects. This study aimed to assess the in vitro antioxidant properties of the methanol extracts from the aerial parts of A. cucullata (ACME) and A. sieheana (ASME) against hydrogen peroxide (H2O2)-induced oxidative stress in human SH-SY5Y neuronal cells. Our study showed that the ACME and ASME provided neuroprotection against H2O2-induced oxidative stress. In conclusion, ACME and ASME might help in reducing oxidative stress for preventive therapy associated with neurodegenerative diseases and cancer. Full article
Open AccessAbstract
Natural Bio-Inks for 3D Bioprinting of Cancer Tumor Models
Proceedings 2019, 40(1), 44; https://doi.org/10.3390/proceedings2019040044 - 19 Jan 2020
Viewed by 184
Abstract
The engineering of convenient three-dimensional (3D) in vitro tumor models presents many challenges, but they are increasingly identifying as one of the best preclinical drug-screening platforms and a developed method to research cancer in controlled conditions in the lab. Recently advanced 3D bioprinting [...] Read more.
The engineering of convenient three-dimensional (3D) in vitro tumor models presents many challenges, but they are increasingly identifying as one of the best preclinical drug-screening platforms and a developed method to research cancer in controlled conditions in the lab. Recently advanced 3D bioprinting techniques can be enhanced to produce biomimetic and complex tumor structures. The native tumors have complex structures originating from different extracellular matrix materials, cell types, and biomolecules. To obtain this, multifactorial bio-inks to consist of multiple hydrogel biomaterials (alginate, collagen, fibrin, gelatin, and chitosan as natural bio-inks), patient-derived different types of cancer cells, and soluble factors have been advanced. 3D bioprinting of live human cells has shown that effective in vitro replication of tumor biology is achievable. Several last research outline current improvements in the use of bio-printed tumor models used in cancer research, enhancing a new boundary for the understanding of tumor biology and the progress of cancer therapies. Full article
Open AccessAbstract
Target Misfolded Protein Clearance Pathway for Cancer Therapy
Proceedings 2019, 40(1), 45; https://doi.org/10.3390/proceedings2019040045 - 24 Jan 2020
Viewed by 202
Abstract
The role of RNA-dependent protein kinase R (PKR) and its association with misfolded protein expression in cancer cells are unclear. Herein we report that PKR regulates misfolded protein clearance by preventing it release through exosomes and promoting lysosomal degradation of misfolded prion proteins [...] Read more.
The role of RNA-dependent protein kinase R (PKR) and its association with misfolded protein expression in cancer cells are unclear. Herein we report that PKR regulates misfolded protein clearance by preventing it release through exosomes and promoting lysosomal degradation of misfolded prion proteins in cancer cells. We demonstrated that PKR contributes to the lysosome function and regulates misfolded prion protein clearance. We hypothesized that PKR-associated lysosome function is critical for cancer but not normal cell survival, representing an effective approach for highly targeted cancer therapy. In screening a compound library, we identified two PKR-associated compound 1 did not affect normal cells but selectively induced cell death in cancer cells depending on their PKR expression status. Pac 1 significantly inhibited the growth of human lung and breast xenograft tumors in mice with no toxicity. Pac 1 binds to PI4K2A and disrupts the PKR/PI4K2A associated lysosome complex, contributing to destabilization of cancer cell lysosomes and triggering cell death. We observed that PKR and PI4K2A play significant prognostic roles in breast cancer patients. These results demonstrate that targeting of a PI4K2A/PKR lysosome complex may be an effective approach for cancer therapy. Full article
Open AccessExtended Abstract
Synthesis of Copper Ion Incorporated Xanthine Oxidase-Based Hybrid Nanoflowers
Proceedings 2019, 40(1), 46; https://doi.org/10.3390/proceedings2019040046 - 08 Feb 2020
Viewed by 179
Abstract
Enzyme has been unique properties due to superior catalytic. [...] Full article
Open AccessAbstract
A New Pain Killer from the Nature: N-Type Calcium Channels Blockers
Proceedings 2019, 40(1), 47; https://doi.org/10.3390/proceedings2019040047 - 08 Feb 2020
Viewed by 180
Abstract
N-type calcium channels (Neuronal-type Calcium channel, Cav2.2) is a member of high voltage activated calcium channels. There are two native small peptides for N-type calcium channels (NTCC) directly which are derived from cone snail, ω-conotoxin-GVIA isolated from Conus geographus and ω-conotoxin-MVIIA (SNX-111, Ziconotide, [...] Read more.
N-type calcium channels (Neuronal-type Calcium channel, Cav2.2) is a member of high voltage activated calcium channels. There are two native small peptides for N-type calcium channels (NTCC) directly which are derived from cone snail, ω-conotoxin-GVIA isolated from Conus geographus and ω-conotoxin-MVIIA (SNX-111, Ziconotide, PrialtTM), from Conus magus which both directly block the α1-ion conducting pore. NTCCs, have been shown to play a key role in nociceptive transmission due to their strategic location, presynaptically in afferent C & Aᵹ fiber terminals and postsynaptically in descending neuron. NTCCs, which are highly expressed at the pre-synaptic terminals of nociceptive neurons in dorsal horn of the spinal cord regulate release of the key pro-nociceptive neurotransmitters such as glutamate, substance P, neurokinin A, and CGRP. There have been many preclinical studies demonstrating the effect of different NTCC blockers in various acute, inflammatory and neuropathic animal pain models. In 2004 ziconotide has been approved in US and Europe to be used in clinical practice. Furthermore, many clinical trials have been performed in more than 1000 patients studying the efficacy and safety of ziconotide. IT administrated of ziconotide showed significant decrease in pain scores in patients with malignant and nonmalignant pain which are practically in neuropathic pain characteristic and resistant to IT opioids. Full article
Open AccessAbstract
Development of Targeted Therapies for Breast and Highly Aggressive Cancers
Proceedings 2019, 40(1), 48; https://doi.org/10.3390/proceedings2019040048 - 08 Feb 2020
Viewed by 178
Abstract
Cancer is one of the top two causes of deaths in the US and the world. Cancer therapy includes standard therapies such as surgery, chemotherapy and targeted therapies, by antibody and small molecule inhibitors, and immunotherapy (i.e., check point inhibitors, CAR-T cell therapy). [...] Read more.
Cancer is one of the top two causes of deaths in the US and the world. Cancer therapy includes standard therapies such as surgery, chemotherapy and targeted therapies, by antibody and small molecule inhibitors, and immunotherapy (i.e., check point inhibitors, CAR-T cell therapy). More recently RNA-based targeted therapeutics were approved by FDA. Although there are about more than 100 targeted therapies, due to significant heterogeneity in patient tumors even in the same subtype of cancers, only faction of patient can benefit from targeted therapies due to lack of target expression in all patients. For some therapeutic targets, such as the most famous and one of the first identified oncogenes, KRAS, which is also considered as an “undrugabale” target expressed in cytoplasm and cannot be targeted by antibodies and small molecule inhibitors, currently there is no FDA approved inhibitors for patients. Therefore, gene targeted and RNA therapies overcome difficulties faced by the use of small molecule and antibodies provide promising new avenue for targeting these oncogenes. After several decades of research finally some of the gene targeted therapies emerged and are being tested in clinical trials. The talk will also give background in targeted therapies used in cancer patients and our novel targeted therapies. After overweening targeted therapies including gene therapies used in cancer with “pros of cons”, my talk will focus on development of RNA, noncoding RNA, small molecule and natural compound-based targeted therapies on the several highly aggressive cancers including triple negative breast cancer, pancreatic, and lung cancer. We discovered and validated EF2 Kinase as a novel molecular target and showed their clinical significance by demonstrating their association with significantly shorter patient survival in TNBC. Using in vitro and in vivo tumor models in mice, we demonstrated that EF2-Kinase regulates, cell proliferation, invasion, and tumorigenesis and nanotherapeutics approaches for targeting EF2-Kinase is highly effective for treatment of patients with highly aggressive cancers. Full article
Open AccessAbstract
Genistein in Prostate Cancer Prevention and Treatment
Proceedings 2019, 40(1), 49; https://doi.org/10.3390/proceedings2019040049 - 09 Feb 2020
Viewed by 191
Abstract
Botanical compounds have been found to modulate genetic and epigenetic pathways of cancer development and progression. We have studied nutritional interventions, with emphasis on soy isoflavones. Preclinical and clinical translational research have been conducted investigating the potential use of natural compounds, particularly soy [...] Read more.
Botanical compounds have been found to modulate genetic and epigenetic pathways of cancer development and progression. We have studied nutritional interventions, with emphasis on soy isoflavones. Preclinical and clinical translational research have been conducted investigating the potential use of natural compounds, particularly soy isoflavones, in the prevention and treatment of cancer. Clinical trials with soy isoflavones in prostate cancer patients have shown that they are potent anti-cancer agents that may be useful in preventing and slowing the progression of prostate cancer. Soy isoflavones could also prevent chemotherapy and radiation therapy toxicities. Furthermore, soy isoflavones may enhance the efficacy of chemotherapy and radiation therapy in patients with prostate cancer. Soy food intake has been associated with a low risk of several cancers. In addition, soy food consumption during cancer treatment may result in better outcomes and longer survival. These observations led to in vitro and in vivo mechanistic studies to elucidate the biological actions of various compounds in soybeans. Soy isoflavones have been found to have profound biological effects and modulate many of the pathways involved in cancer development and progression. In addition to their selective estrogen receptor modulatory effects, these compounds have anti-oxidant, anti-inflammatory and epigenetic effects, which may explain their potential role in cancer prevention and treatment. Soy foods and soy isoflavones can be easily taken together with conventional cancer treatments such as surgery, radiation, chemotherapy, hormone therapy, targeted agents and immunotherapeutic agents. They may enhance the efficacy and reduce the toxicities of radiation therapy, chemotherapy, hormone therapy and other conventional cancer treatments. Natural products such as soy isoflavones could be used to improve treatment effects and quality of life of patients. Soy isoflavones should be investigated in symptom control, quality of life, palliative care and survivorship research. Full article
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