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Resveratrol Down-regulates Bmi-1 Expression and Inhibits Breast Cancer Cell Growth In Vitro

유방암세포 성장과 Bmi-1 발현에 대한 레스베라트롤의 억제 효과

  • Park, Hyun-Joo (Department of Dental Pharmacology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Bak, Kwang Je (Department of Dental Pharmacology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Ok, Chang Youp (Department of Life Science in Dentistry, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Jang, Hye-Ock (Department of Dental Pharmacology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Bae, Moon-Kyoung (Department of Oral Physiology, School of Dentistry, Yangsan Campus of Pusan National University) ;
  • Bae, Soo-Kyung (Department of Dental Pharmacology, School of Dentistry, Yangsan Campus of Pusan National University)
  • 박현주 (부산대학교 치의과전문대학원 치의학과 치과약리학교실) ;
  • 박광제 (부산대학교 치의과전문대학원 치의학과 치과약리학교실) ;
  • 옥창엽 (부산대학교 치의과전문대학원 치의생명과학과) ;
  • 장혜옥 (부산대학교 치의과전문대학원 치의학과 치과약리학교실) ;
  • 배문경 (부산대학교 치의과전문대학원 치의학과 구강생리학교실) ;
  • 배수경 (부산대학교 치의과전문대학원 치의학과 치과약리학교실)
  • Received : 2017.08.20
  • Accepted : 2017.09.12
  • Published : 2017.09.30

Abstract

Resveratrol has been actively investigated as an anticancer drug since it induces cell growth inhibition and apoptosis in many cancer cells. Resveratrol acts through modulation of multiple pathways and genes. In this study, we found resveratrol reduced cell growth and mammosphere formation in MDA-MB-231 triple-negative human breast cancer cells. This suppressive effect of resveratrol is accompanied by a reduction in Bmi-1 gene expression. We also observed that knock-down of Bmi-1 gene by small interfering RNA effectively sensitizes breast cancer cells to resveratrol treatment. Our data demonstrate, for the first time, that resveratrol down-regulates Bmi-1 expression in human breast cancer cells and suggest that specific molecular targeting of Bmi-1 can be combined with a chemotherapeutic strategy to improve the response of breast cancer cells to resveratrol.

Keywords

Acknowledgement

Supported by : 부산대학교

References

  1. Le Du, F., B. L. Eckhardt, B. Lim, J. K. Litton, S. Moulder, F. Meric-Bernstam, A. M. Gonzalez-Angulo, and N. T. Ueno (2015) Is the future of personalized therapy in triple-negative breast cancer based on molecular subtype? Oncotarget. 6: 12890-12908.
  2. Mazzucchelli, S., M. Truffi, F. Baccarini, M. Beretta, L. Sorrentino, M. Bellini, M. A. Rizzuto, R. Ottria, A. Ravelli, P. Ciuffreda, D. Prosperi, and F. Corsi (2017) H-Ferritin-nanocaged olaparib: a promising choice for both BRCA-mutated and sporadic triple negative breast cancer. Sci. Rep. 7: 7505. https://doi.org/10.1038/s41598-017-07617-7
  3. Bayraktar, S. and S. Gluck (2013) Molecularly targeted therapies for metastatic triple-negative breast cancer. Breast Cancer Res. Treat. 138: 21-35. https://doi.org/10.1007/s10549-013-2421-5
  4. Vinod, B. S., H. H. Nair, V. Vijayakurup, A. Shabna, S. Shah, A. Krishna, K. S. Pillai, S. Thankachan, and R. J. Anto (2015) Resveratrol chemosensitizes HER-2-overexpressing breast cancer cells to docetaxel chemoresistance by inhibiting docetaxel-mediated activation of HER-2-Akt axis. Cell Death Discov. 1: 15061. https://doi.org/10.1038/cddiscovery.2015.61
  5. Sprouse, A. A. and B. S. Herbert (2014) Resveratrol augments paclitaxel treatment in MDA-MB-231 and paclitaxel-resistant MDA-MB-231 breast cancer cells. Anticancer Res. 34: 5363-5374.
  6. Cal, C., H. Garban, A. Jazirehi, C. Yeh, Y. Mizutani, and B. Bonavida (2003) Resveratrol and cancer: chemoprevention, apoptosis, and chemo-immunosensitizing activities. Curr. Med. Chem. Anticancer Agents. 3: 77-93. https://doi.org/10.2174/1568011033353443
  7. Langcake, P. and R. J. Pryce (1976) The production of resveratrol by Vitis vinifera and other members of the Vitaceae as a response to infection or injury. Physiol. Plant Pathol. 9: 77-86. https://doi.org/10.1016/0048-4059(76)90077-1
  8. Soleas, G. J., E. P. Diamandis, and DM Goldberg (1997) Resveratrol: a molecule whose time has come? And gone? Clin. Biochem. 30: 91-113. https://doi.org/10.1016/S0009-9120(96)00155-5
  9. Fremont, L. (2000) Biological effects of resveratrol. Life Sci. 66: 663-673. https://doi.org/10.1016/S0024-3205(99)00410-5
  10. Pervaiz, S. and A. L. Holme (2009) Resveratrol: Its biologic targets and functional activity. Antioxid. Redox. Signal. 11: 2851-2897. https://doi.org/10.1089/ars.2008.2412
  11. Sinha, D., N. Sarkar, J. Biswas, and A. Bishayee (2016) Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms. Semin. Cancer Biol. 40-41: 209-232. https://doi.org/10.1016/j.semcancer.2015.11.001
  12. Aluyen, J. K., Q. N. Ton, T. Tran, A. E. Yang, H. B. Gottlieb, and R. A. Bellanger (2012) Resveratrol: potential as anticancer agent. J. Diet Suppl. 9: 45-56. https://doi.org/10.3109/19390211.2011.650842
  13. Shindikar, A., A. Singh, M. Nobre, and S. Kirolikar (2016) Curcumin and resveratrol as promising natural remedies with nanomedicine approach for the effective treatment of triple negative breast cancer. J. Oncol. 2016: 9750785.
  14. Rai, G., S. Suman, S. Mishra, and Y. Shukla (2017) Evaluation of growth inhibitory response of Resveratrol and Salinomycin combinations against triple negative breast cancer cells. Biomed. Pharmacother. 89:1142-1151. https://doi.org/10.1016/j.biopha.2017.02.110
  15. Aluyen, J. K., Q. N. Ton, T. Tran, A. E. Yang, H. B. Gottlieb, and R. A. Bellanger (2012) Resveratrol: Potential as anticancer agent. J. Diet Suppl. 9: 45-56. https://doi.org/10.3109/19390211.2011.650842
  16. Schech, A. J., A. A. Kazi, R. A. Gilani, and A. H. Brodie (2013) Zoledronic acid reverses the epithelial-mesenchymal transition and inhibits self-renewal of breast cancer cells through inactivation of $NF-{\kappa}B$. Mol. Cancer Ther. 12: 1356-1366. https://doi.org/10.1158/1535-7163.MCT-12-0304
  17. Pan, J., J. Shen, W. Si, C. Du, D. Chen, L. Xu, M. Yao, P. Fu, and W. Fan (2017) Resveratrol promotes MICA/B expression and natural killer cell lysis of breast cancer cells by suppressing c-Myc/ miR-17 pathway. Oncotarget.
  18. Benetatos, L., G. Vartholomatos, and E. Hatzi-michael (2014) Polycomb group proteins and MYC: The cancer connection. Cell Mol. Life Sci. 71: 257-269. https://doi.org/10.1007/s00018-013-1426-x
  19. van Lohuizen, M., S. Verbeek, B. Scheijen, E. Wientjens, H. van der Gulden and A. Berns (1991) Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging. Cell 65: 737-752. https://doi.org/10.1016/0092-8674(91)90382-9
  20. Siddique, H. R. and M. Saleem (2012) Role of BMI1, a stem cell factor, in cancer recurrence and chemoresistance: preclinical and clinical evidences. Stem Cells. 30: 372-378. https://doi.org/10.1002/stem.1035
  21. Honig, A., C. Weidler, S. Hausler, M. Krockenberger, S. Buchholz, F. Koster, S. E. Segerer, J. Dietl, and J. B. Engel (2010) Overexpression of polycomb protein BMI-1 in human specimens of breast, ovarian, endometrial and cervical cancer. Anticancer Res. 30:1559-1564.
  22. Zheng, X., Y. Wang, B. Liu, C. Liu, D. Liu, J. Zhu, C. Yang, J. Yan, X. Liao, X. Meng, and H. Yang (2014) Bmi-1-shRNA inhibits the proliferation of lung adenocarcinoma cells by blocking the G1/S phase through decreasing cyclin D1 and increasing p21/p27 levels. Nucleic Acid Ther. 24: 210-216. https://doi.org/10.1089/nat.2013.0459
  23. Xu, Z., H. Liu, X. Lv, Y. Liu, S. Li, and H. Li (2011) Knockdown of the Bmi-1 oncogene inhibits cell proliferation and induces cell apoptosis and is involved in the decrease of Akt phosphorylation in the human breast carcinoma cell line MCF-7. Oncol. Rep. 25: 409-418.
  24. Wang, Y. D., Y. J. Su, J. Y. Li, X. C. Yao, and G. J. Liang (2015) Rapamycin, a mTOR inhibitor, induced growth inhibition in retinoblastoma Y79 cell via down-regulation of Bmi-1. Int. J. Clin. Exp. Pathol. 8: 5182-5188.
  25. Deng, W., Y. Zhou, A. F. Tiwari, H. Su, J. Yang, V. M. Zhu, D. Lau, P. M. Hau, Y. L. Yip, A. L. Cheung, X. Y. Guan, and S. W. Tsao (2015) p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells. Int. J. Cancer 136: 1361-1370. https://doi.org/10.1002/ijc.29114
  26. Qin, L., X. Zhang, L. Zhang, Y. Feng, G. X. Weng, M. Z. Li, Q. L. Kong, C. N. Qian, Y. X. Zeng, M. S. Zeng, D. F. Liao, and L. B. Song (2008) Downregulation of BMI-1 enhances 5-fluorouracil-induced apoptosis in nasopharyngeal carcinoma cells. Biochem. Biophys. Res. Commun. 371: 531-535. https://doi.org/10.1016/j.bbrc.2008.04.117
  27. Wu, X., X. Liu, J. Sengupta, Y. Bu, F. Yi, C. Wang, Y. Shi, Y. Zhu, Q. Jiao, and F. Song (2011) Silencing of Bmi-1 gene by RNA interference enhances sensitivity to doxorubicin in breast cancer cells. Indian J. Exp. Biol. 49: 105-112.
  28. Gieni, R. S., I. H. Ismail, S. Campbell, and M. J. Hendzel (2011) Polycomb group proteins in the DNA damage response: A link between radiation resistance and "stemness". Cell Cycle 10: 883-894. https://doi.org/10.4161/cc.10.6.14907
  29. Liu, Z. G., L. Liu, L. H. Xu, W. Yi, Y. L. Tao, Z. W. Tu, M. Z. Li, M. S. Zeng, and Y. F. Xia (2012) Bmi-1 induces radioresistance in MCF-7 mammary carcinoma cells. Oncol. Rep. 27: 1116-1122. https://doi.org/10.3892/or.2011.1615
  30. Lanzilli, G., M. P. Fuggetta, M. Tricarico, A. Cottarelli, A. Serafino, R. Falchetti, G. Ravagnan, M. Turriziani, R. Adamo, O. Franzese, and E. Bonmassar (2006) Resveratrol down-regulates the growth and telomerase activity of breast cancer cells in vitro. Int. J. Oncol. 28: 641-648.
  31. Liu, S., G. Dontu, I. D. Mantle, S. Patel, N. S. Ahn, K. W. Jackson, P. Suri, and M. S. Wicha (2006) Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 66: 6063-6071. https://doi.org/10.1158/0008-5472.CAN-06-0054