Myricetin Inhibits Proliferation of Cisplatin-resistant Cancer Cells Through a P53-dependent Apoptotic Pathway

Overview

Journal Int J Oncol

Specialty Oncology

Date 2015 Aug 29

PMID 26315556

Citations 24

Authors

Haizhi Huang

Allen Y Chen

Xingqian Ye

Bingyun Li

Yon Rojanasakul

Gary O Rankin

Yi Charlie Chen

Affiliations

Soon will be listed here.

Abstract

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatin-resistant cancer cell lines, but did not induce apoptosis in the normal ovarian cell line. It induced both Bcl-2 family-dependent intrinsic and DR5 dependent extrinsic apoptosis in OVCAR-3 cells. P53, a multifunctional tumor suppressor, regulated apoptosis in OVCAR-3 cells through a Bcl-2 family protein-dependent pathway. Myricetin did not induce cell cycle arrest in either ovarian cancer cell line. Because of its potency and selectivity against cisplatin-resistant cancer cells, myricetin could potentially be used to overcome cancer chemoresistance against platinum-based therapy.

Citing Articles

Selected Flavonols Targeting Cell Death Pathways in Cancer Therapy: The Latest Achievements in Research on Apoptosis, Autophagy, Necroptosis, Pyroptosis, Ferroptosis, and Cuproptosis.

Wendlocha D, Kubina R, Krzykawski K, Mielczarek-Palacz A Nutrients. 2024; 16(8).

PMID: 38674891 PMC: 11053927. DOI: 10.3390/nu16081201.

Selected Flavonols in Breast and Gynecological Cancer: A Systematic Review.

Wendlocha D, Krzykawski K, Mielczarek-Palacz A, Kubina R Nutrients. 2023; 15(13).

PMID: 37447264 PMC: 10346890. DOI: 10.3390/nu15132938.

Myricetin: a potential plant-derived anticancer bioactive compound-an updated overview.

Kumar S, Swamy N, Tuli H, Rani S, Garg A, Mishra D Naunyn Schmiedebergs Arch Pharmacol. 2023; 396(10):2179-2196.

PMID: 37083713 DOI: 10.1007/s00210-023-02479-5.

Why Do Dietary Flavonoids Have a Promising Effect as Enhancers of Anthracyclines? Hydroxyl Substituents, Bioavailability and Biological Activity.

Golonko A, Olichwier A, Swislocka R, Szczerbinski L, Lewandowski W Int J Mol Sci. 2023; 24(1).

PMID: 36613834 PMC: 9820151. DOI: 10.3390/ijms24010391.

Unravelling Potential Health-Beneficial Properties of Phenolic Compounds: A Systematic Review.

Cerquido A, Vojtek M, Ribeiro-Oliveira R, Viegas O, Sousa J, Ferreira I Pharmaceuticals (Basel). 2022; 15(10).

PMID: 36297345 PMC: 9610266. DOI: 10.3390/ph15101231.

References

Gartel A, Radhakrishnan S . Lost in transcription: p21 repression, mechanisms, and consequences. Cancer Res. 2005; 65(10):3980-5. DOI: 10.1158/0008-5472.CAN-04-3995. View

Ho J, Ma W, Mao D, Benchimol S . p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle arrest. Mol Cell Biol. 2005; 25(17):7423-31. PMC: 1190302. DOI: 10.1128/MCB.25.17.7423-7431.2005. View

Kuo Y, Kuo P, Hsu Y, Cho C, Lin C . Ellipticine induces apoptosis through p53-dependent pathway in human hepatocellular carcinoma HepG2 cells. Life Sci. 2005; 78(22):2550-7. DOI: 10.1016/j.lfs.2005.10.041. View

Zhang X, Zou Z, Xu C, Shen Y, Li D . Myricetin induces G2/M phase arrest in HepG2 cells by inhibiting the activity of the cyclin B/Cdc2 complex. Mol Med Rep. 2011; 4(2):273-7. DOI: 10.3892/mmr.2011.417. View

Stordal B, Davey M . Understanding cisplatin resistance using cellular models. IUBMB Life. 2007; 59(11):696-9. DOI: 10.1080/15216540701636287. View

Yang Y, Kim J, Lee K, Choi J . Costunolide induces apoptosis in platinum-resistant human ovarian cancer cells by generating reactive oxygen species. Gynecol Oncol. 2011; 123(3):588-96. DOI: 10.1016/j.ygyno.2011.08.031. View

Windsor R, Strauss S, Kallis C, Wood N, Whelan J . Germline genetic polymorphisms may influence chemotherapy response and disease outcome in osteosarcoma: a pilot study. Cancer. 2011; 118(7):1856-67. DOI: 10.1002/cncr.26472. View

Kong D, Ma S, Liang B, Yi H, Zhao Y, Xin R . The different regulatory effects of p53 status on multidrug resistance are determined by autophagy in ovarian cancer cells. Biomed Pharmacother. 2012; 66(4):271-8. DOI: 10.1016/j.biopha.2011.12.002. View

Guan Y, Li Z, Yang A, Huang Z, Zheng Z, Zhang L . Cell cycle arrest and apoptosis of OVCAR-3 and MCF-7 cells induced by co-immobilized TNF-α plus IFN-γ on polystyrene and the role of p53 activation. Biomaterials. 2012; 33(26):6162-71. DOI: 10.1016/j.biomaterials.2012.05.037. View

10.

Hall M, Okabe M, Shen D, Liang X, Gottesman M . The role of cellular accumulation in determining sensitivity to platinum-based chemotherapy. Annu Rev Pharmacol Toxicol. 2007; 48:495-535. DOI: 10.1146/annurev.pharmtox.48.080907.180426. View

11.

Darcy K, Brady W, McBroom J, Bell J, Young R, McGuire W . Associations between p53 overexpression and multiple measures of clinical outcome in high-risk, early stage or suboptimally-resected, advanced stage epithelial ovarian cancers A Gynecologic Oncology Group study. Gynecol Oncol. 2008; 111(3):487-95. PMC: 2615492. DOI: 10.1016/j.ygyno.2008.08.020. View

12.

Brunelle J, Letai A . Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci. 2009; 122(Pt 4):437-41. PMC: 2714431. DOI: 10.1242/jcs.031682. View

13.

Gates M, Vitonis A, Tworoger S, Rosner B, Titus-Ernstoff L, Hankinson S . Flavonoid intake and ovarian cancer risk in a population-based case-control study. Int J Cancer. 2009; 124(8):1918-25. PMC: 2703422. DOI: 10.1002/ijc.24151. View

14.

Wilson T, Johnston P, Longley D . Anti-apoptotic mechanisms of drug resistance in cancer. Curr Cancer Drug Targets. 2009; 9(3):307-19. DOI: 10.2174/156800909788166547. View

15.

Phillips P, Sangwan V, Borja-Cacho D, Dudeja V, Vickers S, Saluja A . Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Cancer Lett. 2011; 308(2):181-8. PMC: 3126884. DOI: 10.1016/j.canlet.2011.05.002. View

16.

Liu T, Hannafon B, Gill L, Kelly W, Benbrook D . Flex-Hets differentially induce apoptosis in cancer over normal cells by directly targeting mitochondria. Mol Cancer Ther. 2007; 6(6):1814-22. PMC: 2701109. DOI: 10.1158/1535-7163.MCT-06-0279. View

17.

Basli A, Soulet S, Chaher N, Merillon J, Chibane M, Monti J . Wine polyphenols: potential agents in neuroprotection. Oxid Med Cell Longev. 2012; 2012:805762. PMC: 3399511. DOI: 10.1155/2012/805762. View

18.

Diaz-Moralli S, Tarrado-Castellarnau M, Miranda A, Cascante M . Targeting cell cycle regulation in cancer therapy. Pharmacol Ther. 2013; 138(2):255-71. DOI: 10.1016/j.pharmthera.2013.01.011. View

19.

Shiomi K, Kuriyama I, Yoshida H, Mizushina Y . Inhibitory effects of myricetin on mammalian DNA polymerase, topoisomerase and human cancer cell proliferation. Food Chem. 2013; 139(1-4):910-8. DOI: 10.1016/j.foodchem.2013.01.009. View

20.

Zhang X, Chen S, Tang L, Shen Y, Luo L, Xu C . Myricetin induces apoptosis in HepG2 cells through Akt/p70S6K/bad signaling and mitochondrial apoptotic pathway. Anticancer Agents Med Chem. 2013; 13(10):1575-81. DOI: 10.2174/1871520613666131125123059. View