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Special Issue "Natural Products: Anticancer Potential and Beyond"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: 15 December 2017

Special Issue Editors

Guest Editor
Dr. Zhe-Sheng (Jason) Chen

Department of Pharmaceutical Sciences, St. John's University, Queens, USA
Website | E-Mail
Interests: Drug Resistance; ABC transporters; Cancer Chemotherapy; Natural Products; Nanomaterials
Guest Editor
Dr. Dong-Hua Yang

Department of Pharmaceutical Sciences, St. John's University, Queens, USA
E-Mail
Interests: Biomarkers; Anti-Cancer Drugs; Cancer Chemotherapy; Cancer Biology; Developmental Biology

Special Issue Information

Dear Colleagues,

In the period of 1981–2010, about 80% of the anticancer drugs approved for clinical use were either natural products or inspired by natural products, highlighting the importance of natural products in cancer treatment. Indeed, many natural products have been introduced into oncological practice and also used as lead compounds for the development of more potent and less toxic anticancer drugs. Many natural product anticancer drugs, including those from plants (e.g., vincristine, paclitaxel, irrinotecan, etoposide, etc.), marine sources (e.g., cytarabine), and microbials (e.g., dactinomycine, doxorubicin, bleomycins, etc.), are currently used in clinics. In this Special Issue, we invite investigators to contribute original research articles, as well as review articles that are related to the application of natural products in the treatment of cancer. We are particularly interested in research that works toward improving the anticancer effects of natural products while reducing their side effects. Potential topics include, but are not limited to:

• The anti-cancer effects of new natural products, and their underlying mechanisms
• Pharmacological interventions for the treatment of cancer in natural products
• The development of new natural products that reverse multi-drug resistance in cancer
• Clinical studies and therapeutic efficacy in anti-cancer natural products.

Dr. Zhe-Sheng (Jason) Chen
Dr. Dong-Hua Yang
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Natural products
  • Anti-cancer
  • Chemotherapy
  • Drug Resistance
  • ABC transporters
  • P-glycoprotein
  • Breast cancer resistance protein
  • Side effects
  • Marine drugs
  • Plants
  • Microbials
  • Isolation
  • Extracts

Published Papers (14 papers)

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Research

Open AccessArticle ‘Click Chemistry’ Synthesis of Novel Natural Product-Like Caged Xanthones Bearing a 1,2,3-Triazole Moiety with Improved Druglike Properties as Orally Active Antitumor Agents
Molecules 2017, 22(11), 1834; doi:10.3390/molecules22111834
Received: 12 October 2017 / Revised: 26 October 2017 / Accepted: 26 October 2017 / Published: 27 October 2017
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Abstract
DDO-6101, a natural-product-like caged xanthone discovered previously in our laboratory based on the pharmacophoric scaffold of the Garcinia natural product gambogic acid (GA), shows potent cytotoxicity in vitro, but poor efficacy in vivo due to its poor druglike properties. In order to
[...] Read more.
DDO-6101, a natural-product-like caged xanthone discovered previously in our laboratory based on the pharmacophoric scaffold of the Garcinia natural product gambogic acid (GA), shows potent cytotoxicity in vitro, but poor efficacy in vivo due to its poor druglike properties. In order to improve the druglike properties and in vivo antitumor potency, a novel series of ten triazole-bearing caged xanthone derivatives of DDO-6101 has been efficiently synthesized by ‘click chemistry’ and evaluated for their in vitro antitumor activity and druglike properties. Most of the target compounds have sustained cytotoxicity against A549, HepG2, HCT116, and U2OS cancer cells and possess improved aqueous solubility, as well as permeability. Notably, these caged xanthones are also active towards taxol-resistant or cisplatin-resistant A549 cancer cells. Taking both the in vitro activities and druglike properties into consideration, compound 8g has been advanced into in vivo efficacy experiments. The results reveal that 8g (named as DDO-6318), both by intravenous or per os administration, are much more potent than the lead DDO-6101 in A549-transplanted mice models and it could be a promising antitumor candidate for further evaluation. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessArticle Phaseolus acutifolius Lectin Fractions Exhibit Apoptotic Effects on Colon Cancer: Preclinical Studies Using Dimethilhydrazine or Azoxi-Methane as Cancer Induction Agents
Molecules 2017, 22(10), 1670; doi:10.3390/molecules22101670
Received: 24 August 2017 / Revised: 28 September 2017 / Accepted: 28 September 2017 / Published: 8 October 2017
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Abstract
Phaseolus acutifolius (Tepary bean) lectins have been studied as cytotoxic molecules on colon cancer cells. The toxicological profile of a Tepary bean lectin fraction (TBLF) has shown low toxicity in experimental animals; exhibiting anti-nutritional effects such as a reduction in body weight gain
[...] Read more.
Phaseolus acutifolius (Tepary bean) lectins have been studied as cytotoxic molecules on colon cancer cells. The toxicological profile of a Tepary bean lectin fraction (TBLF) has shown low toxicity in experimental animals; exhibiting anti-nutritional effects such as a reduction in body weight gain and a decrease in food intake when using a dose of 50 mg/kg on alternate days for six weeks. Taking this information into account, the focus of this work was to evaluate the effect of the TBLF on colon cancer using 1,2-dimethylhydrazine (DMH) or azoxy-methane/dextran sodium sulfate (AOM/DSS) as colon cancer inductors. Rats were treated with DMH or AOM/DSS and then administered with TBFL (50 mg/kg) for six weeks. TBLF significantly decreased early tumorigenesis triggered by DMH by 70%, but without any evidence of an apoptotic effect. In an independent experiment, AOM/DSS was used to generate aberrant cryptic foci, which decreased by 50% after TBLF treatment. TBLF exhibited antiproliferative and proapoptotic effects related to a decrease of the signal transduction pathway protein Akt in its activated form and an increase of caspase 3 activity, but not to p53 activation. Further studies will deepen our knowledge of specific apoptosis pathways and cellular stress processes such as oxidative damage. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessArticle Therapeutic Mechanisms of Vernonia amygdalina Delile in the Treatment of Prostate Cancer
Molecules 2017, 22(10), 1594; doi:10.3390/molecules22101594
Received: 28 August 2017 / Revised: 19 September 2017 / Accepted: 19 September 2017 / Published: 22 September 2017
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Abstract
Prostate cancer patients have been suffering from limited treatment options due to late diagnosis, poor drug tolerance, and multi-drug resistance to almost all the current drug treatments. Therefore, it is important to seek a new alternative therapeutic medicine that can effectively prevent the
[...] Read more.
Prostate cancer patients have been suffering from limited treatment options due to late diagnosis, poor drug tolerance, and multi-drug resistance to almost all the current drug treatments. Therefore, it is important to seek a new alternative therapeutic medicine that can effectively prevent the disease and even eradicate the progression and metastasis of prostate cancer. Vernonia amygdalina Delile (VAD) is a common edible vegetable in Cameroon that has been used as a traditional medicine for some human diseases. However, to the best of our knowledge, no previous reports have explored its therapeutic efficacy against human prostate cancer. The objective of the present study was to assess the anticancer activities of VAD methanolic extracts in the prevention and treatment of prostate cancer using human androgen-independent prostate cancer (PC-3) cells as a test model. To achieve our objective, PC-3 cells were treated with various doses of VAD for 48 h. Data generated from the trypan blue test and MTT assay demonstrated that VAD extracts exhibited significant growth-inhibitory effects on PC-3 cells. Collectively, we established for the first time the antiproliferative effects of VAD on PC-3 cells, with an IC50 value of about 196.6 µg/mL. Further experiments, including cell morphology, lipid peroxidation and comet assays, and apoptosis analysis showed that VAD caused growth-inhibitory effects on PC-3 cells through the induction of cell growth arrest, DNA damage, apoptosis, and necrosis in vitro and may provide protection from oxidative stress diseases as a result of its high antioxidant content. These results provide useful data on the anticancer activities of VAD for prostate cancer and demonstrate the novel possibilities of this medicinal plant for developing prostate cancer therapies. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessArticle Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice
Molecules 2017, 22(10), 1593; doi:10.3390/molecules22101593
Received: 30 July 2017 / Revised: 9 September 2017 / Accepted: 19 September 2017 / Published: 22 September 2017
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Abstract
Colorectal cancer (CRC) is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO)
[...] Read more.
Colorectal cancer (CRC) is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO) on the progression of colon carcinogenesis in ApcMin/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet) for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of β-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of β-catenin, cyclinD1, c-myc and p-GSK-3β in HCT116 and SW480 cells at 25 μM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessArticle Cytotoxic and Hypoglycemic Activity of Triterpenoid Saponins from Camellia oleifera Abel. Seed Pomace
Molecules 2017, 22(10), 1562; doi:10.3390/molecules22101562
Received: 19 July 2017 / Revised: 14 September 2017 / Accepted: 15 September 2017 / Published: 21 September 2017
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Abstract
One new and three known triterpenoid saponins were isolated and identified from Camellia oleifera seeds through IR, NMR, HR-ESI-MS and GC-MS spectroscopic methods, namely oleiferasaponin A3, oleiferasaponin A1, camelliasaponin B1, and camelliasaponin B2. The structure
[...] Read more.
One new and three known triterpenoid saponins were isolated and identified from Camellia oleifera seeds through IR, NMR, HR-ESI-MS and GC-MS spectroscopic methods, namely oleiferasaponin A3, oleiferasaponin A1, camelliasaponin B1, and camelliasaponin B2. The structure of oleiferasaponin A3 was elucidated as 16α-hydroxy-21β-O-angeloyl-22α-O-cinnamoyl-23α-aldehyde-28-dihydroxymethylene-olean-12-ene-3β-O-[β-d-galactopyranosyl-(1→2)]-[β-d-xylopyranosyl-(1→2)-β-d-galactopyranosyl-(1→3)]-β-d-gluco-pyranosiduronic acid. Camelliasaponin B1 and camelliasaponin B2 exhibited potent cytotoxic activity on three human tumour cell lines (human lung tumour cells (A549), human liver tumour cells (HepG2), cervical tumour cells (Hela)). The hypoglycemic activity of oleiferasaponin A1 was testified by protecting pancreatic β-cell lines from high-glucose damage. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessFeature PaperArticle Cytotoxic and Apoptotic Activities of Prunus spinosa Trigno Ecotype Extract on Human Cancer Cells
Molecules 2017, 22(9), 1578; doi:10.3390/molecules22091578
Received: 8 August 2017 / Accepted: 17 September 2017 / Published: 20 September 2017
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Abstract
The aim of this work was to demonstrate that a natural compound, not-toxic to normal cells, has cytotoxic and sensitizing effects on carcinoma cells, with the final goal of combining it with chemotherapeutic drugs to reduce the overall dose. Prunus spinosa Trigno ecotype
[...] Read more.
The aim of this work was to demonstrate that a natural compound, not-toxic to normal cells, has cytotoxic and sensitizing effects on carcinoma cells, with the final goal of combining it with chemotherapeutic drugs to reduce the overall dose. Prunus spinosa Trigno ecotype (PsT) drupe extract with a nutraceutical activator complex (NAC) made of amino acids, vitamins and mineral salt blends, has shown in vitro anticancer activity. The cytotoxic effect of (PsT + NAC)® has been evaluated on human cancer cells, with an initial screening with colorectal, uterine cervical, and bronchoalveolar cells, and a subsequent focus on colon carcinoma cells HCT116 and SW480. The viability reduction of HCT116 and SW480 after treatment with (PsT 10 mg/mL + NAC)® was about 40% (p < 0.05), compared to control cells. The cell’s survival reduction was ineffective when the drug vehicle (NAC) was replaced with a phosphate buffer saline (PBS) or physiological solution (PS). The flow cytometry evaluation of cancer cells’ mitochondrial membrane potential showed an increase of 20% depolarized mitochondria. Cell cycle analysis showed a sub G1 (Gap 1 phase) peak appearance (HCT116: 35.1%; SW480: 11.6%), indicating apoptotic cell death induction that was confirmed by Annexin V assay (HCT116: 86%; SW480: 96%). Normal cells were not altered by (PsT + NAC)® treatments. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessArticle Arenobufagin Induces Apoptotic Cell Death in Human Non-Small-Cell Lung Cancer Cells via the Noxa-Related Pathway
Molecules 2017, 22(9), 1525; doi:10.3390/molecules22091525
Received: 9 August 2017 / Revised: 2 September 2017 / Accepted: 8 September 2017 / Published: 11 September 2017
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Abstract
Arenobufagin, an active component isolated from the traditional Chinese medicine Chan Su, exhibits anticancer influences in several human malignancies. However, the effects and action mechanisms of arenobufagin on non-small-cell lung cancer (NSCLC) are still unknown. In this study, we reported that arenobufagin acted
[...] Read more.
Arenobufagin, an active component isolated from the traditional Chinese medicine Chan Su, exhibits anticancer influences in several human malignancies. However, the effects and action mechanisms of arenobufagin on non-small-cell lung cancer (NSCLC) are still unknown. In this study, we reported that arenobufagin acted through activation of Noxa-related pathways and promoted apoptotic cell death in human NSCLC cells. Our results revealed that arenobufagin-induced apoptosis was caspase-dependent, as evidenced by the fact that caspase-9, caspase-3 and poly (ADP-ribose) polymerase (PARP) were cleaved, and pretreatment with a pan-caspase inhibitor Z-VAD-FMK inhibited the pro-apoptosis effect of arenobufagin. Mechanistically, we further found that arenobufagin rapidly upregulated the expression of the pro-apoptosis protein Noxa, and abrogated the anti-apoptosis protein Mcl-1, a major binding partner of Noxa in the cell. More importantly, the knockdown of Noxa greatly blocked arenobufagin-induced cell death, highlighting the contribution of this protein in the anti-NSCLC effects of arenobufagin. Interestingly, arenobufagin also increased the expression of p53, a direct transcriptional activator for the upregulation of the Noxa protein. Taken together, our results suggest that arenobufagin is a potential anti-NSCLC agent that triggers apoptotic cell death in NSCLC cells through interfering with the Noxa-related pathway. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessArticle Ginger Phytochemicals Inhibit Cell Growth and Modulate Drug Resistance Factors in Docetaxel Resistant Prostate Cancer Cell
Molecules 2017, 22(9), 1477; doi:10.3390/molecules22091477
Received: 1 August 2017 / Accepted: 2 September 2017 / Published: 5 September 2017
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Abstract
Ginger has many bioactive compounds with pharmacological activities. However, few studies are known about these bioactive compounds activity in chemoresistant cells. The aim of the present study was to investigate the anticancer properties of ginger phytochemicals in docetaxel-resistant human prostate cancer cells in
[...] Read more.
Ginger has many bioactive compounds with pharmacological activities. However, few studies are known about these bioactive compounds activity in chemoresistant cells. The aim of the present study was to investigate the anticancer properties of ginger phytochemicals in docetaxel-resistant human prostate cancer cells in vitro. In this study, we isolated 6-gingerol, 10-gingerol, 4-shogaol, 6-shogaol, 10-shogaol, and 6-dehydrogingerdione from ginger. Further, the antiproliferation activity of these compounds was examined in docetaxel-resistant (PC3R) and sensitive (PC3) human prostate cancer cell lines. 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol at the concentration of 100 μM significantly inhibited the proliferation in PC3R but 6-gingerol, 6-shogaol, and 10-shogaol displayed similar activity in PC3. The protein expression of multidrug resistance associated protein 1 (MRP1) and glutathione-S-transferase (GSTπ) is higher in PC3R than in PC3. In summary, we isolated the bioactive compounds from ginger. Our results showed that 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol inhibit the proliferation of PC3R cells through the downregulation of MRP1 and GSTπ protein expression. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessArticle Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake
Molecules 2017, 22(9), 1444; doi:10.3390/molecules22091444
Received: 3 August 2017 / Revised: 28 August 2017 / Accepted: 29 August 2017 / Published: 31 August 2017
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Abstract
Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in
[...] Read more.
Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidrug resistant cell lines. However, the mechanism of action (MOA) of ADR’s anticancer and anti-drug-resistance activities remain elusive. Methods: In this study, we used the MV4-11 cell line, a FLT3 positive acute myeloid leukemia (AML) cell line that displays multidrug resistance, as our experimental system. We first evaluated the effect of ADR on MV4-11 cell proliferation. Then, a quantitative proteomics approach was applied to identify differentially expressed proteins in ADR-treated MV4-11 cells. Finally, cellular processes and signal pathways affected by ADR in MV4-11 cell were predicted with proteomic analysis and validated with in vitro assays. Results: ADR inhibits MV4-11 cell proliferation in a dose- and time-dependent manner. With a proteomic approach, we discovered that ADR inhibited fatty acid synthesis, cellular iron uptake and FLT3 signaling pathway in MV4-11 cells. Conclusions: ADR inhibits MV4-11 cell proliferation through inhibition of fatty acid synthesis, iron uptake and protein synthesis. Furthermore, ADR reduces drug resistance by blocking FLT3 signaling. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessArticle Cytotoxic Activity of Origanum Vulgare L. on Hepatocellular Carcinoma cell Line HepG2 and Evaluation of its Biological Activity
Molecules 2017, 22(9), 1435; doi:10.3390/molecules22091435
Received: 1 August 2017 / Revised: 22 August 2017 / Accepted: 29 August 2017 / Published: 30 August 2017
Cited by 2 | PDF Full-text (2657 KB) | HTML Full-text | XML Full-text
Abstract
The potential of plant essential oils (EOs) in anticancer treatment has recently received many research efforts to overcome the development of multidrug resistance and their negative side effects. The aims of the current research are to study (i) the cytotoxic effect of the
[...] Read more.
The potential of plant essential oils (EOs) in anticancer treatment has recently received many research efforts to overcome the development of multidrug resistance and their negative side effects. The aims of the current research are to study (i) the cytotoxic effect of the crude EO extracted from Origanum vulgare subsp hirtum and its main constituents (carvacrol, thymol, citral and limonene) on hepatocarcinoma HepG2 and healthy human renal cells HEK293; (ii) the antibacterial and phytotoxic activities of the above EO and its main constituents. Results showed that cell viability percentage of treated HepG2 by EO and its main constituents was significantly decreased when compared to untreated cells. The calculated inhibition concentration (IC50) values for HepG2 were lower than healthy renal cells, indicating the sort of selectivity of the studied substances. Citral is not potentially recommended as an anticancer therapeutic agent, since there are no significant differences between IC50 values against both tested cell lines. Results showed also that oregano EO and its main constituents have a significant antibacterial activity and a moderate phytotoxic effect. The current research verified that oregano EO and its main constituents could be potentially utilized as anticancer therapeutic agents. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessArticle Structure Identification and In Vitro Anticancer Activity of Lathyrol-3-phenylacetate-5,15-diacetate
Molecules 2017, 22(9), 1412; doi:10.3390/molecules22091412
Received: 7 August 2017 / Accepted: 22 August 2017 / Published: 25 August 2017
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Abstract
Natural products from the genus Euphorbia show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining
[...] Read more.
Natural products from the genus Euphorbia show attention-attracting activities, such as anticancer activity. In this article, classical isolation and structure identification were used in a study on Caper Euphorbia Seed. Subsequently, MTT and wound healing assays, flow cytometry, western blotting, Hoechst 33258 staining and fluorescence microscopy examination were applied to investigate the anticancer activity of the obtained compounds. In a result, lathyrol-3-phenyl- acetate-5,15-diacetate (deoxy Euphorbia factor L1, DEFL1) was isolated from Caper Euphorbia Seed. Moreover, the NMR signals were totally assigned. DEFL1 showed potent inhibition against lung cancer A549 cells, with an IC50 value of 17.51 ± 0.85 μM. Furthermore, DEFL1 suppressed wound healing of A549 cells in a concentration-dependent manner. Mechanically, DEFL1 induced apoptosis, with involvement of an increase of reactive oxygen species (ROS), decrease of mitochondrial membrane potential (ΔΨm), release of cytochrome c, activity raise of caspase-9 and 3. Characteristic features of apoptosis were observed by fluorescence microscopy. In summary, DEFL1 inhibited growth and induced apoptosis in lung cancer A549 cells via a mitochondrial pathway. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessArticle Interaction of Flavonoids from Woodwardia unigemmata with Bovine Serum Albumin (BSA): Application of Spectroscopic Techniques and Molecular Modeling Methods
Molecules 2017, 22(8), 1317; doi:10.3390/molecules22081317
Received: 6 July 2017 / Revised: 31 July 2017 / Accepted: 4 August 2017 / Published: 9 August 2017
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Abstract
Phytochemical investigation on the methanol extract of Woodwardia unigemmata resulted in the isolation of seven flavonoids, including one new flavonol acylglycoside (1). The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis and comparison of literature data.
[...] Read more.
Phytochemical investigation on the methanol extract of Woodwardia unigemmata resulted in the isolation of seven flavonoids, including one new flavonol acylglycoside (1). The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis and comparison of literature data. The multidrug resistance (MDR) reversing activity was evaluated for the isolated compounds using doxorubicin-resistant K562/A02 cells model. Compound 6 showed comparable MDR reversing effect to verapamil. Furthermore, the interaction between compounds and bovine serum albumin (BSA) was investigated by spectroscopic methods, including steady-state fluorescence, synchronous fluorescence, circular dichroism (CD) spectroscopies, and molecular docking approach. The experimental results indicated that the seven flavonoids bind to BSA by static quenching mechanisms. The negative ΔH and ΔS values indicated that van der Waals interactions and hydrogen bonds contributed in the binding of compounds 26 to BSA. In the case of compounds 1 and 7 systems, the hydrophobic interactions play a major role. The binding of compounds to BSA causes slight changes in the secondary structure of BSA. There are two binding sites of compound 6 on BSA and site I is the main site according to the molecular docking studies and the site marker competitive binding assay. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessArticle γ-Tocotrienol Inhibits Proliferation and Induces Apoptosis via the Mitochondrial Pathway in Human Cervical Cancer HeLa Cells
Molecules 2017, 22(8), 1299; doi:10.3390/molecules22081299
Received: 10 July 2017 / Revised: 28 July 2017 / Accepted: 2 August 2017 / Published: 4 August 2017
PDF Full-text (5063 KB) | HTML Full-text | XML Full-text
Abstract
γ-Tocotrienol, a kind of isoprenoid phytochemical, has antitumor activity. However, there is limited evidence that it has an effect on cervical cancer. In this study, the capacity to inhibit proliferation and induce apoptosis in human cervical cancer HeLa cells and the mechanism underlying
[...] Read more.
γ-Tocotrienol, a kind of isoprenoid phytochemical, has antitumor activity. However, there is limited evidence that it has an effect on cervical cancer. In this study, the capacity to inhibit proliferation and induce apoptosis in human cervical cancer HeLa cells and the mechanism underlying these effects were examined. The results indicated that a γ-tocotrienol concentration over 30 μM inhibited the growth of HeLa cells with a 50% inhibitory concentration (IC50) of 46.90 ± 3.50 μM at 24 h, and significantly down-regulated the expression of proliferative cell nuclear antigen (PCNA) and Ki-67. DNA flow cytometric analysis indicated that γ-tocotrienol arrested the cell cycle at G0/G1 phase and reduced the S phase in HeLa cells. γ-tocotrienol induced apoptosis of HeLa cells in a time- and dose-dependent manner. γ-tocotrienol-induced apoptosis in HeLa cells was accompanied by down-regulation of Bcl-2, up-regulation of Bax, release of cytochrome from mitochondria, activation of caspase-9 and caspase-3, and subsequent poly (ADP-ribose) polymerase (PARP) cleavage. These results suggested that γ-tocotrienol could significantly inhibit cell proliferation through G0/G1 cell cycle arrest, and induce apoptosis via the mitochondrial apoptotic pathway in human cervical cancer HeLa cells. Thus, our findings revealed that γ-tocotrienol may be considered as a potential agent for cervical cancer therapy. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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Open AccessArticle Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells
Molecules 2017, 22(8), 1285; doi:10.3390/molecules22081285
Received: 17 July 2017 / Accepted: 31 July 2017 / Published: 2 August 2017
Cited by 1 | PDF Full-text (2254 KB) | HTML Full-text | XML Full-text
Abstract
Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly induced sub-G1
[...] Read more.
Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP), which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (z-VAD-fmk) inhibited fisetin-induced apoptosis. In addition, fisetin induced death receptor 5 (DR5) expression at the transcriptional level, and down-regulation of DR5 by siRNA blocked fisetin-induced apoptosis. Furthermore, fisetin induced p53 protein expression through up-regulation of protein stability, whereas down-regulation of p53 by siRNA markedly inhibited fisetin-induced DR5 expression. In contrast, fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis. Taken together, our study demonstrates that fisetin induced apoptosis through p53 mediated up-regulation of DR5 expression at the transcriptional level. Full article
(This article belongs to the Special Issue Natural Products: Anticancer Potential and Beyond)
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