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A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Bioorganic Chemistry and Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 18612

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Dr. Won Sup Lee

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Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea
Interests: tumor suppressor gene; oncogene; phytochemials; targeted approach; cell death; molecular mechanisms; cancer therapy
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Special Issue Information

Dear Colleagues,
Cancer is a deadly disease. Not only can it take the life of the patient, but it can also destroy the lives of family and friends who try to be caregivers for the patient. This disease starts with the accumulation of genetic changes in cells that affect cell growth and survival. Cancer cells acquire the ability to grow uncontrollably, invade normal tissues, and then spread into nearby or distant organs. Then, the cells can destroy multiple organs and finally take the life of a person.
Phytochemicals are chemicals of plant origin. They generally help plants resist competitors, pathogens, or predators. Evidence suggests that some of them show anticancer effects in terms of proliferation, survival, invasion, and metastasis of cancer. We also know that phytochemicals are very important resources for anticancer drug development.
Therefore, this Special Issue is dedicated to original research articles, short communications, and reviews which cover the latest findings on the role of phytochemicals in the prevention and treatment of cancer.
The scope of the special issue
1. role of phytochemicals in carcinogenesis
2. role of phytochemicals in chemoprevention
3. role of phytochemicals in cancer treatment as anticancer agents
4. role of phytochemicals in cancer treatment as an enhancer of certain chemotherapeutic agents
5. characterized bioactive components from a natural plant extract showing anticancer effects
Authors are invited to submit original articles, short communications, and reviews related to the abovementioned topics

Dr. Won Sup Lee
Guest Editor

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Keywords

cancer
phytochemicals
chemoprevention
anticancer effects
signaling mechanisms

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Published Papers (7 papers)

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Research

18 pages, 1969 KiB

Open AccessArticle

Cell Growth Inhibition, DNA Fragmentation and Apoptosis-Inducing Properties of Household-Processed Leaves and Seeds of Fenugreek (Trigonella Foenum-Graecum Linn.) against HepG2, HCT-116, and MCF-7 Cancerous Cell Lines

by Shaimaa G. Abdel Salam, Mohamed M. Rashed, Nabih A. Ibrahim, Emam A. Abdel Rahim, Hadeil Muhanna Alsufiani, Rasha A. Mansouri, Mohamed Afifi and Ammar Al-Farga

Curr. Issues Mol. Biol. 2023, 45(2), 936-953; https://doi.org/10.3390/cimb45020060 - 19 Jan 2023

Cited by 5 | Viewed by 2247

Abstract

Household processing of fenugreek seeds and leaves, including soaking, germination, and boiling of the seeds, and air-drying of the leaves, has improved the levels of human consumption of the bitter seeds and increased the shelf life of fresh leaves, respectively. The potential anticancer activity of either unprocessed or processed fenugreek seeds or leaves and the relative expression of pro-apoptotic and anti-apoptotic genes of the studied cancerous cell lines exposed to IC₅₀ crude extracts was investigated to observe the apoptotic-inducing property of this plant as an anticancer agent. The protein expression of IKK-α and IKK-β, as inhibitors of NF-KB which exhibit a critical function in the regulation of genes involved in chronic inflammatory disorders, were studied in the tested cancerous cell lines. In this study, the anticancer activity of household-processed fenugreek leaves and seeds against HepG2, HCT-116, MCF-7, and VERO cell lines was measured using an MTT assay. DNA fragmentation of both HepG2 and MCF-7 was investigated by using gel electrophoresis. RT-PCR was used to evaluate the relative expression of each p53, caspase-3, Bax, and Bcl-2 genes, whereas ELISA assay determined the expression of caspase-3, TNF-α, and 8-OHDG genes. Western blotting analyzed the protein-expressing levels of IKK-α and IKK-β proteins in each studied cell line. Data showed that at 500 µg mL⁻¹, ADFL had the highest cytotoxicity against the HepG2 and HCT-116 cell lines. Although, each UFS and GFS sample had a more inhibitory effect on MCF-7 cells than ADFL. Gel electrophoresis demonstrated that the IC₅₀ of each ADFL, UFS, and GFS sample induced DNA fragmentation in HepG2 and MCF-7, contrary to untreated cell lines. Gene expression using RT-PCR showed that IC₅₀ doses of each sample induced apoptosis through the up-regulation of the p53, caspase-3, and Bax genes and the down-regulation of the Bcl-2 gene in each studied cell line. The relative expression of TNF-α, 8-OHDG, and caspase-3 genes of each HepG2 and MCF-7 cell line using ELISA assays demonstrated that ADFL, UFS, and GFS samples reduced the expression of TNF-α and 8-OHDG genes but increased the expression of the caspase-3 gene. Protein-expressing levels of IKK-α and IKK-β proteins in each studied cell line, determined using Western blotting, indicated that household treatments decreased IKK-α expression compared to the UFS sample. Moreover, the ADFL and SFS samples had the most activity in the IKK-β expression levels. Among all studied samples, air-dried fenugreek leaves and unprocessed and germinated fenugreek seeds had the most anti-proliferative and apoptotic-inducing properties against human HepG2, MCF-7, and HCT-116 cell lines, as compared to the VERO cell line. So, these crude extracts can be used in the future for developing new effective natural drugs for the treatment of hepatocellular, breast, and colon carcinomas. Full article

(This article belongs to the Special Issue New Sights: Phytochemicals and Cancer)

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18 pages, 8080 KiB

Open AccessArticle

Chemopreventive Effects of Onosma mutabilis against Azoxymethane-Induced Colon Cancer in Rats via Amendment of Bax/Bcl-2 and NF-κB Signaling Pathways

by Ahmed Aj. Jabbar, Ibrahim Abdel Aziz Ibrahim, Fuad O. Abdullah, Kareem Fattah Aziz, Abdullah R. Alzahrani and Mahmood Ameen Abdulla

Curr. Issues Mol. Biol. 2023, 45(2), 885-902; https://doi.org/10.3390/cimb45020057 - 18 Jan 2023

Cited by 13 | Viewed by 2599

Abstract

Onosma species (Boraginaceae) are well known as medicinal plants due to their wide range of pharmaceutical potential. The present study aims to investigate the anticancer (in vitro) and chemo-protective (in vivo) efficacies of Onosma mutabilis extract (OME) in the azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats. The in vitro antiproliferative effects of OME were determined on two human tumor cell lines (Caco-2 and HT-29) via MTT assay. The in vivo chemoprotective effects of OME were investigated by performing various biochemical analyses in serum and tissue homogenates of albino rats, along with determining oxidative stress biomarkers. Inflammatory biomarkers of colon, colonic gross morphology (by methylene blue), ACF formation, and colonic histopathology (H & E stain) were determined. The immunohistochemistry of colonic tissues was also assessed by Bax and Bcl-2 protein expression. The results showed that the antitumor activity of OME against Caco-2 and HT-29 colorectal cancer cells ranged between 22.28–36.55 µg/mL. OME supplementation caused a significant drop in the ACF values and improved the immunohistochemistry of the rats shown by up-regulation of Bax and down-regulation of Bcl-2 protein expressions. These outcomes reveal that O. mutabilis may have chemoprotective efficiency against AOM-induced colon cancer represented by the attenuation of ACF formation possibly through inhibition of free radicals, inflammation, and stimulation of the colon antioxidant armory (SOD, CAT, and GPx) and positive regulation of the Nrf2-Keap1 pathway. Full article

(This article belongs to the Special Issue New Sights: Phytochemicals and Cancer)

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11 pages, 3352 KiB

Open AccessArticle

Induction of Apoptosis and Effect on the FAK/AKT/mTOR Signal Pathway by Evodiamine in Gastric Cancer Cells

by Ji Yeong Yang, Hyun Jun Woo, Pyeongjae Lee and Sa-Hyun Kim

Curr. Issues Mol. Biol. 2022, 44(9), 4339-4349; https://doi.org/10.3390/cimb44090298 - 19 Sep 2022

Cited by 7 | Viewed by 2149

Abstract

Evodiamine isolated from Evodia rutaecarpa has been known to have anti-tumor activity against various cancer cell types. Although there have been reports showing the inhibitory effect of evodiamine on cell survival of gastric cancer cell, it is not clearly explained how evodiamine affects the expression and modification of proteins associated with apoptosis and upstream signal pathways. We confirmed the cytotoxic activity of evodiamine against AGS and MKN45 cells by a WST assay, cell morphological change, and clonogenic assay. The apoptotic cells were evaluated by Annexin V/PI analysis and Western blot and the expressions of apoptosis-related molecules were confirmed by Western blot. Evodiamine promoted apoptosis of AGS gastric cancer cells through both intrinsic and extrinsic signal pathways in a time- and dose-dependent manner. Evodiamine attenuated the expression of anti-apoptotic proteins, including Bcl-2, XIAP, and survivin, and elevated that of the pro-apoptotic protein Bax. Evodiamine also suppressed the FAK/AKT/mTOR signal pathway. Based on these results, we expect that the results from this study will further elucidate our understanding of evodiamine as an anti-cancer drug. Full article

(This article belongs to the Special Issue New Sights: Phytochemicals and Cancer)

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21 pages, 1164 KiB

Open AccessArticle

Anticancer Secondary Metabolites: From Ethnopharmacology and Identification in Native Complexes to Biotechnological Studies in Species of Genus Astragalus L. and Gloriosa L.

by Iliana Ionkova, Aleksandar Shkondrov, Yancho Zarev, Ekaterina Kozuharova and Ilina Krasteva

Curr. Issues Mol. Biol. 2022, 44(9), 3884-3904; https://doi.org/10.3390/cimb44090267 - 26 Aug 2022

Cited by 11 | Viewed by 2945

Abstract

Some of the most effective anticancer compounds are still derived from plants since the chemical synthesis of chiral molecules is not economically efficient. Rapid discovery of lead compounds with pronounced biological activity is essential for the successful development of novel drug candidates. This work aims to present the chemical diversity of antitumor bioactive compounds and biotechnological approaches as alternative production and sustainable plant biodiversity conservation. Astragalus spp., (Fabaceae) and Gloriosa spp. (Liliaceae) are selected as research objects within this review because they are known for their anticancer activity, because they represent two of the largest families respectively in dicots and monocots, and also because many of the medicinally important plants are rare and endangered. We summarized the ethnobotanical data concerning their anticancer application, highlighted the diversity of their secondary metabolites possessing anticancer properties such as saponins, flavonoids, and alkaloids, and revealed the potential of the in vitro cultures as an alternative way of their production. Since the natural supply is limited, it is important to explore the possibility of employing plant cell or organ in vitro cultures for the biotechnological production of these compounds as an alternative. Full article

(This article belongs to the Special Issue New Sights: Phytochemicals and Cancer)

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15 pages, 2608 KiB

Open AccessArticle

Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest

by Claudia Vanessa Arellano-Gutiérrez, Laura Itzel Quintas-Granados, Hernán Cortés, Manuel González del Carmen, Gerardo Leyva-Gómez, Lilia Patricia Bustamante-Montes, Miguel Rodríguez-Morales, Israel López-Reyes, Juan Ramón Padilla-Mendoza, Lorena Rodríguez-Páez, Gabriela Figueroa-González and Octavio Daniel Reyes-Hernández

Curr. Issues Mol. Biol. 2022, 44(5), 2054-2068; https://doi.org/10.3390/cimb44050139 - 8 May 2022

Cited by 8 | Viewed by 2989

Abstract

Cervical cancer (CC) is one of the most common cancers in women, and is linked to human papillomavirus (HPV) infection. The virus oncoprotein E6 binds to p53, resulting in its degradation and allowing uncontrolled cell proliferation. Meanwhile, the HPV E7 protein maintains host cell differentiation by targeting retinoblastoma tumor suppressor. The host cell can ubiquitinate E6 and E7 through UBE2L3, whose expression depends on the interaction between the aryl hydrocarbon receptor (AhR) with Xenobiotic Responsive Elements (XREs) located in the UBE2L3 gene promoter. In this study, we used cell culture to determine the effect of indole-3-carbinol (I3C) over cellular viability, apoptosis, cell proliferation, and mRNA levels of UBE2L3 and CYP1A1. In addition, patients’ samples were used to determine the mRNA levels of UBE2L3 and CYP1A1 genes. We found that I3C promotes the activation of AhR and decreases cell proliferation, possibly through UBE2L3 mRNA induction, which would result in the ubiquitination of HPV E7. Since there is a strong requirement for selective and cost-effective cancer treatments, natural AhR ligands such as I3C could represent a novel strategy for cancer treatment. Full article

(This article belongs to the Special Issue New Sights: Phytochemicals and Cancer)

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20 pages, 7222 KiB

Open AccessArticle

Cold Atmospheric Plasma-Activated Media Improve Paclitaxel Efficacy on Breast Cancer Cells in a Combined Treatment Model

by Cosmin-Teodor Mihai, Ilarion Mihaila, Maria Antoanela Pasare, Robert Mihai Pintilie, Mitica Ciorpac and Ionut Topala

Curr. Issues Mol. Biol. 2022, 44(5), 1995-2014; https://doi.org/10.3390/cimb44050135 - 30 Apr 2022

Cited by 10 | Viewed by 2453

Abstract

The use of plasma-activated media (PAM), an alternative to direct delivery of cold atmospheric plasma to cancer cells, has recently gained interest in the plasma medicine field. Paclitaxel (PTX) is used as a chemotherapy of choice for various types of breast cancers, which is the leading cause of mortality in females due to cancer. In this study, we evaluated an alternative way to improve anti-cancerous efficiency of PTX by association with PAM, the ultimate achievement being a better outcome in killing tumoral cells at smaller doses of PTX. MCF-7 and MDA-MB-231 cell lines were used, and the outcome was measured by cell viability (MTT assay), the survival rate (clonogenic assay), apoptosis occurrence, and genotoxicity (COMET assay). Treatment consisted of the use of PAM in combination with under IC50 doses of PTX in short- and long-term models. The experimental data showed that PAM had the capacity to improve PTX’s cytotoxicity, as viability of the breast cancer cells dropped, an effect maintained in long-term experiments. A higher frequency of apoptotic, dead cells, and DNA fragmentation was registered in cells treated with the combined treatment as compared with those treated only with PT. Overall, PAM had the capacity to amplify the anti-cancerous effect of PTX. Full article

(This article belongs to the Special Issue New Sights: Phytochemicals and Cancer)

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11 pages, 3100 KiB

Open AccessArticle

Chrysophanol Suppresses Cell Growth via mTOR/PPAR-α Regulation and ROS Accumulation in Cultured Human Tongue Squamous Carcinoma SAS Cells

by Po-Chih Hsu, Chia-Chen Hsu, Yi-Jan Hsia and Chan-Yen Kuo

Curr. Issues Mol. Biol. 2022, 44(4), 1528-1538; https://doi.org/10.3390/cimb44040104 - 1 Apr 2022

Cited by 5 | Viewed by 2322

Abstract

Oral cancer, a type of head and neck cancer, can pose a significant risk of death unless diagnosed and treated early. Alternative treatments are urgently needed owing to the high mortality rate, limitations of conventional treatments, and many complications. The anthraquinone compound chrysophanol acts as a tumor suppressor on some types of cancer cells. To date, it has not been clarified how chrysophanol affects human tongue squamous carcinoma. This study was aimed to examine the effects of chrysophanol on oral cancer treatment. The results show that chrysophanol caused cell death, reduced the expression of the mammalian target of rapamycin (mTOR)/peroxisome proliferator-activated receptor-alpha (PPAR-α), and increased reactive oxygen species (ROS) production. We also used two ion chelators, deferoxamine (DFO) and liproxstatin-1 (Lipro), to further determine whether chrysophanol inhibits cell growth and regulates mTOR/PPAR-α expression and ROS production, both of which are involved in iron homeostasis. The results show that DFO and Lipro reversed the increase in cell death, downregulation of mTOR/PPAR-α, and decrease in ROS accumulation. In conclusion, chrysophanol inhibits the growth of oral squamous cell carcinoma cells by modulating mTOR/PPAR-α and by causing ROS accumulation. Full article

(This article belongs to the Special Issue New Sights: Phytochemicals and Cancer)

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