Expression of genes modulated by epigallocatechin-3-gallate in breast cancer cells

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Summary

Introduction: Breast cancer is the most common malignant cancer among women. Both drug resistance and metastasis are major problems in the treatment of breast cancer. Therefore, adjuvant therapy may improve patients’ survival and affect their quality of life. It is suggested that epigallocatechin gallate (EGCG) which is well known for its chemopreventive activity and acts on numerous molecular targets may inhibit the growth and metastasis of some cancers. Hence, discovering the metastatic molecular mechanisms for breast cancer may be useful for therapy.

Objective: The aim of the study was to determine the effect of EGGC on the mRNA expression level of genes such as ZEB1, ABCB1, MDM2, TWIST1 and PTEN in MCF-7 breast cancer cells.

Methods: MCF7/DOX were cultured in the presence of 0.2 μM DOX and EGCG (20-50 μM). The mRNA expression level was determined by real-time quantitative PCR using RealTime ready Custom Panel 96 kit.

Results: Our results showed an important increase (about 2-fold for 20 μM EGCG + 0.2 μM DOX and 2.5-fold for 50 μM EGCG + 0.2 μM DOX, p<0.05) in ZEB1 expression levels. In case of ABCB1 gene lack of influence on the mRNA level was observed (p>0.05). We also observed significant decrease of ZEB1 expression in MCF7 cells with 20 μM and 50 μM EGCG (p<0.05). In addition, EGCG (20 μM) caused an increase of MDM2 and PTEN mRNA levels in almost 100% (p<0.05) and 40% (p>0.05), respectively. Lack of the influence of EGCG was noted for the TWIST1 gene expression. In case of MCF7/DOX we showed an increase of mRNA level of PTEN gene about 50% (p<0.05).

Conclusions: These results suggest that EGCG may be potentially used in adjuvant therapy in the breast cancer treatment.

1. Radecka B, Litwiniuk M. Breast cancer in young women. Ginekol Pol 2016; 87(9):659-663. doi: http://dx.doi.org/10.5603/GP.2016.0062

2. Siegel R, Jiemin MA, Zhaohui Z, Jemal A. Cancer statistics. Cancer J Clin 2014; 64(1):9-29. doi: http://dx.doi.org/10.3322/caac.21208

3. Liu RH. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr 2003; 78:517S–520S. doi: http://dx.doi.org/10.1093/ajcn/78.3.517S

4. Liu RH. Whole grain phytochemicals and health. J Cereal Sci 2007; 46(3):207-219.

5. Liu RH. Health-promoting components of fruits and vegetables in the diet. Adv Nutr 2013; 4(3):384S–392S. doi: http://dx.doi.org/10.3945/an.112.003517

6. Huang WY, Cai YZ, Zhang Y. Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutr Cancer 2009; 62(1):1-20. doi: http://dx.doi.org/10.1080/01635580903191585

7. Efferth T, Li PC, Konkimalla VS, Kaina B. From traditional Chinese medicine to rational cancer therapy. Trends Mol Med 2007; 13(8):353-361. doi: http://dx.doi.org/10.1016/j.molmed.2007.07.001

8. Tapas A, Sakarkar D, Kakde R. Flavonoids as nutraceuticals: A review. Herba Pol 2010; 56(2):105-117.

9. Ramos S. Cancer chemoprevention and chemo-therapy: dietary polyphenols and signalling pathways. Mol Nutr Food Res 2008; 52(5):507-526. doi: http://dx.doi.org/10.1002/mnfr.200700326

10. Sen T, Dutta A, Chatterjee A. Epigallocatechin-3-gallate (EGCG) downregulates gelatinase-B (MMP-9) by involvement of FAK/ERK/NFkappaB and AP-1 in the human breast cancer cell line MDA-MB-231. Anticancer Drugs 2010; 21(6):632-644.

11. Stefaniak A, Sytykiewicz H, Czerniewicz P, Leszczyński B. Catechin-like antioxidative potential of selected tea products. Herba Pol 2012; 58(2):17-25.

12. Dube A, Nicolazzo JA, Larson I. Chitosan nanoparticles enhance the intestinal absorption of the green tea catechins (+)-catechin and (−)-epigallocatechin gallate. Eur J Pharma Sci 2010; 41(2):219-225. doi: http://dx.doi.org/10.1016/j.ejps.2010.06.010

13. Stuart EC, Scandlyn MJ, Rosengren RJ. Role of epigallocatechin gallate (EGCG) in the treatment of breast and prostate cancer. Life Sci 2006; 79(25):2329-2336. doi: http://dx.doi.org/10.1016/j.lfs.2006.07.036

14. Mereles D, Hunstein W. Epigallocatechin-3-gallate (EGCG) for clinical trials: more pitfalls than promises? Int J Mol Sci 2011; 12 (9):5592-5603.

15. Klinski E, Semov A, Yan X, Alakhov V., Muyzhnek E., Kiselev V. Block copolymer-based composition of epigallocatechin-3-gallate with improved oral bioavailability as a way to increase its therapeutic activity. J Nanomedicine Bio-therapeutic Disc 2013; 3:117. doi: http://dx.doi.org/10.4172/2155-983X.1000117

16. Luo H, Xu M, Zhong WT, Cui ZY, Liu FM, Zhou KY et al. EGCG decreases the expression of HIF-1α and VEGF and cell growth in MCF-7 breast cancer cells. J BUON. 2013; 19 (2): 435-439.

17. Qin J, Xie LP, Zheng XY, Wang YB, Bai Y, Shen HF et al. A component of green tea, (−)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins. Biochem Biophys Res Commun 2007; 354(4):852-857. doi: http://dx.doi.org/10.1016/j.bbrc.2007.01.003

18. Liang YC, Lin-Shiau SY, Chen CF, Lin JK. Inhibition of cyclin-dependent kinases 2 and 4 activities as well as induction of cdk inhibitors p21 and p27 during growth arrest of human breast carcinoma cells by (−)-epigallocatechin-3-gallate. J Cell Biochem. 1999; 75 (1): 1-12.

19. Sun L, Yuan JM, Koh WP, Yu MC. Green tea, black tea and breast cancer risk: a meta-analysis of epidemiological studies. Carcinogenesis 2006; 27(7):1310-1315. doi: http://dx.doi.org/10.1093/carcin/bgi276

20. Ogunleye AA, Xue F, Michels KB. Green tea consumption and breast cancer risk or recurrence: a meta-analysis. Breast Cancer Res Treat 2010; 119:477-484. doi: http://dx.doi.org/10.1007/s10549-009-0415-0

21. Thangapazham RT, Singh AK, Sharma A, Warren J, Gaddipati JP, Maheshwari RK. Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo. Cancer Lett 2007; 245(1-2):232-241. doi: http://dx.doi.org/10.1016/j.canlet.2006.01.027

22. Tran PL, Kim SA, Choi HS, Yoon JH, Ahn SG. Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo. BMC Cancer 2010; 10:276. doi: http://dx.doi.org/10.1186/1471-2407-10-276

23. Manjegowda MC, Deb G, Kumar N, Limaye AM. Expression profiling of genes modulated by estrogen, EGCG or both in MCF-7 breast cancer cells. Genomics Data 2015; 5:210-212. doi:http://dx.doi.org/10.1016/j.gdata.2015.05.040

24. Bronsert P, Kohler I, Timme S, Kiefer S, Werner M, Schilling O et al. Prognostic significance of Zinc finger E-box binding homeobox 1 (ZEB1) expression in cancer cells and cancer-associated fibroblasts in pancreatic head cancer. Surgery 2014; 156(1):97-108. doi: http://dx.doi.org/10.1016/j.surg.2014.02.018

25. Karihtala P, Auvinen P, Kauppila S, Haapasaari KM, Jukkola-Vuorinen A, Soini Y. Vimentin, zeb1 and Sip1 are up-regulated in triple-negative and basal-like breast cancers: association with an aggressive tumour phenotype. Breast Cancer Res Treat 2013; 138(1):81-90. doi: http://dx.doi.org/10.1007/s10549-013-2442-0

26. Liu Y, Lu X, Huang L, Wang W, Jiang G, Dean KC et al. Different thresholds of ZEB1 are required for Ras-mediated tumour initiation and metastasis. Nat Commun 2014; 5:5660. doi: http://dx.doi.org/10.1038/ncomms6660

27. Brabletz S, Bajdak K, Meidhof S, Burk U, Niedermann G, Firat E et al. The ZEB1/miR-200 feedback loop controls Notch signalling in cancer cells. EMBO J 2011; 30 (4):770-782. doi: http://dx.doi.org/10.1038/emboj.2010.349

28. Zhu Z, Wang Y, Liu Z, Wang F, Zhao Q. Inhibitory effects of epigallocatechin-3-gallate on cell proliferation and the expression of HIF-1α and P-gp in human pancreatic carcinoma cell line PANC-1. Oncol Rep 2012; 27(5):1567-1572. doi: http://dx.doi.org/10.3892/or.2012.1697

29. Lee JT, Gu W. The multiple levels of regulation by p53 ubiquitination. Cell Death Differ. 2010; 17(1):86-92. doi: http://dx.doi.org/10.1038/cdd.2009.77

30. Jin L, Li C, Xu Y, Wang L, Liu J, Wang D et al. Epigallocatechin gallate promotes p53 accumulation and activity via the inhibition of MDM2-mediated p53 ubiquitination in human lung cancer cells. Oncol Rep. 2013; 29(5):1983-1990. doi: http://dx.doi.org/10.3892/or.2013.2343

31. Zhong J, Ogura K, Wang Z, Inuzuka H. Degradation of the transcription factor Twist, an oncoprotein that promotes cancer metastasis. Discov Med 2013; 15(80):7-15.

32. Li Ch, Duan P, Wang J, Lu X, Cheng J. miR-320 inhibited ovarian cancer oncogenicity via targeting TWIST1 expression. Am J Transl Res. 2017; 9(8): 3705-3713.

33. De Amicis F, Perri A, Vizza D, Russo A, Panno ML, Bonofiglio D et al. Epigallocatechin gallate inhibits growth and epithelial-to-mesenchymal transition in human thyroid carcinoma cell lines. J Cell Physiol. 2013; 228(10):2054-2062. doi: http://dx.doi.org/10.1002/jcp.24372

34. Liu S, Xu ZL, Sun L, Liu Y, Li CC, Li HM et al. (-)-Epigallocatechin-3-gallate induces apoptosis in human pancreatic cancer cells via PTEN. Mol Med Rep 2016; 14(1):599-605. doi: http://doi.org/10.3892/mmr.2016.5277

35. Moradzadeh M, Hosseini A, Erfanian S, Rezaei H. Epigallocatechin-3-gallate promotes apoptosis in human breast cancer T47D cells through down-regulation of PI3K/AKT and Telomerase. Pharmacol Rep 2017; 69(5):924-928. doi: http://dx.doi.org/10.1016/j.pharep.2017.04.008

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