Molecular mechanisms underlying anticancer effects of myricetin

Cancer is a devastating disease that has claimed many lives. Natural bioactive agents from plants are gaining wide attention for their anticancer activities. Several studies have found that natural plant-based bioactive compounds can enhance the efficacy of chemotherapy, and in some cases ameliorate some of the side-effects of drugs used as chemotherapeutic agents. In this paper, we have reviewed the literature on the anticancer effects of four plant-based bioactive compounds namely, curcumin, myricetin, geraniin and tocotrienols (T3) to provide an overview on some of the key findings that are related to this effect. The molecular mechanisms through which the active compounds may exert their anticancer properties in cell and animal-based studies also discussed.

https://www.mdpi.com/2218-273X/9/12/758/pdf

Bioactive Compounds: Natural Defense Against Cancer?

Synergy is a process in which some substances cooperate to reach a combined effect that is greater than the sum of their separate effects. It can be considered a natural “straight” strategy which has evolved by nature to obtain more efficacy at low cost. In this regard, synergistic effects may be observed in the interaction between herbal products and conventional drugs or biochemical compounds. It is important to identify and exploit these interactions since any improvement brought by such kind of process can be advantageously used to treat human disorders. Even in a complex disease such as cancer, positive synergistic plant–drug interactions should be investigated to achieve the best outcomes, including providing a greater benefit to patients or avoiding adverse side effects. This review analyzes and summarizes the current knowledge on the synergistic effects of plant–drug interactions with a focus on anticancer strategies.

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Synergistic Effects of Plant Derivatives and Conventional Chemotherapeutic Agents: An Update on the Cancer Perspective

Gynecologic cancers involve the female genital organs, such as the vulva, vagina, cervix, endometrium, ovaries, and fallopian tubes. The occurrence and frequency of gynecologic cancer depends on personal lifestyle, history of exposure to viruses or carcinogens, genetics, body shape, and geographical habitat. For a long time, research into the molecular biology of cancer was broadly restricted to protein-coding genes. Recently it has been realized that non-coding RNAs (ncRNA), including long noncoding RNAs (LncRNAs), microRNAs, circular RNAs and piRNAs (PIWI-interacting RNAs), can all play a role in the regulation of cellular function within gynecological cancer. It is now known that ncRNAs are able to play dual roles, i.e. can exert both oncogenic or tumor suppressive functions in gynecological cancer. Moreover, several clinical trials are underway looking at the biomarker and therapeutic roles of ncRNAs. These efforts may provide a new horizon for the diagnosis and treatment of gynecological cancer. Herein, we summarize some of the ncRNAs that have been shown to be important in gynecological cancers.

Gynecologic cancers and non-coding RNAs: Epigenetic regulators with emerging roles.

A novel rutin-fucoidan complex based phytotherapy for cervical cancer through achieving enhanced bioavailability and cancer cell apoptosis.

Circular RNAs (circRNAs) are group of noncoding RNAs derived from back-splicing events. Accumulating evidence certifies the critical roles of circRNAs in human tumorigenesis. However, the role and biogenesis of circRNAs in cervical cancer are still unclear. Here, a novel identified circRNA, circSLC26A4, was found to be upregulated in cervical cancer tissue and cells. Clinically, the high expression of circSLC26A4 was related to the poor survival of cervical cancer patients. Functionally, cellular experiments indicated that circSLC26A4 knockdown repressed the proliferation, invasion, and tumor growth in vitro and in vivo. Furthermore, circSLC26A4 acted as the sponge of miR-1287-5p; moreover, miR-1287-5p targeted the 3′ UTR of HOXA7 mRNA. Mechanistically, RNA binding protein (RBP) quaking (QKI) was identified to interact with the QKI response elements (QREs) in SLC26A4 gene introns, thereby promoting circSLC26A4 biogenesis. In conclusion, these findings demonstrate that circSLC26A4 facilitates cervical cancer progression through the QKI/circSLC26A4/miR-1287-5p/HOXA7 axis, which might bring novel therapeutic strategies for cervical cancer.

Circular RNA circSLC26A4 Accelerates Cervical Cancer Progression via miR-1287-5p/HOXA7 Axis.

Drug combination therapies are common practice in the treatment of cancer. In this study, we evaluated the anticancer effects of myricetin (MYR), methyl eugenol (MEG) and cisplatin (CP) both separately as well as in combination against cervical cancer (HeLa) cells. To demonstrate whether MYR and MEG enhance the anticancer activity of CP against cervical cancer cells, we treated HeLa cells with MYR and MEG alone or in combination with cisplatin and evaluated cell growth and apoptosis using MTT (3 (4, 5 dimethyl thiazol 2yl) 2, 5 diphenyltetrazolium bromide) assay, LDH release assay, flow cytometry and fluorescence microscopy. The results revealed that, as compared to single drug treatment, the combination of MYR or MEG with CP resulted in greater effect in inhibiting cancer cell growth and inducing apoptosis. Cell apoptosis induction, Caspase-3 activity, cell cycle arrest and mitochondrial membrane potential loss were systematically studied to reveal the mechanisms of synergy between MYR, MEG and CP. Combination of MYR or MEG with CP resulted in more potent apoptosis induction as revealed by fluorescence microscopy using Hoechst 33258 and AO-ETBR staining. The combination treatment also increased the number of cells in G0/G1 phase dramatically as compared to single drug treatment. Mitochondrial membrane potential loss (ΛΨm) as well as Caspase-3 activity was much higher in combination treatment as compared to single drug treatment. Findings of this investigation suggest that MYR and MEG combined with cisplatin is a potential clinical chemotherapeutic approach in human cervical cancer.

Myricetin and methyl eugenol combination enhances the anticancer activity, cell cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer cell lines.

Background Ovarian cancer is one of the six most common women's cancers in the world, and is found among the top three female genital tumors, which is lower than the rate of endometrial cancer and cervical cancer. Methods This study utilized miR-675 mimics and siRNA transfection to construct miR-675 overexpression and lower-expression model to investigate the effect of miR-675 on the regulation of ovarian cancer. Western blotting and RT-qPCR were applied for the quantitative testing of mRNA and protein expression. Apoptosis of podocytes was detected by TUNEL staining. Results H19 expression was also up-regulated. In vitro, H19 silencing after transfection with si-H19 could suppress proliferation and invasion. Luciferase reporter assay revealed a close link between miR-675 and H19 3'-UTR. Furthermore, combining experiments of miR-675 and H19 indicated that miR-675 could reverse the function of H19 on ovarian cancer. Conclusion Our study reveals the overexpression of H19 in ovarian cancer tissue and cells, and discovers an oncogenic role in ovarian cancer via sponging miR-675, providing a potential biomarker for early detection and prognosis of ovarian cancer.

Yan Ding

Papers

Circular RNA circSLC26A4 Accelerates Cervical Cancer Progression via miR-1287-5p/HOXA7 Axis.

Myricetin and methyl eugenol combination enhances the anticancer activity, cell cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer cell lines.

Long non-coding RNA H19 promotes tumorigenesis of ovarian cancer by sponging miR-675.