Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway

  • Authors:
    • Hong Pan
    • Wenbin Zhou
    • Wei He
    • Xiaoan Liu
    • Qiang Ding
    • Lijun Ling
    • Xiaoming Zha
    • Shui Wang
  • View Affiliations

  • Published online on: May 9, 2012
  • Pages: 337-343
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Genistein (Gen) has been reported as a protective factor against breast cancer. However, the molecular mechanism by which Gen elicits its effects on triple-negative breast cancer cells has not been fully elucidated. In our study, the breast cancer cell line MDA-MB-231 was selected to determine the action of Gen on triple-negative breast cancer cells. MTT assay, flow cytometric analysis, siRNA transfection, western blotting and nuclear factor-κB (NF-κB) activation-nuclear translocation assay were used to address the role of NF-κB activity and the Notch-1 signaling pathway on the effects of Gen. Our study revealed that Gen elicited a dramatic effect on cell growth inhibition, in a dose-dependent and time-dependent manner. Treatment of MDA-MB-231 cells with 0, 5, 10 or 20 µM Gen induced apoptosis of 6.78, 18.98, 30.45 and 60.64%, respectively. Exposure of MDA-MB-231 cells to Gen also resulted in G2/M phase accumulation of cells corresponding to 4.93, 12.54, 18.93 and 30.95%, respectively. Furthermore, our data demonstrated for the first time that Gen inhibited the growth of MDA-MB-231 triple-negative breast cancer cells by inhibiting NF-κB activity via the Nocth-1 signaling pathway in a dose-dependent manner. We also found that Gen downregulated the expression of cyclin B1, Bcl-2 and Bcl-xL, possibly mediated by NF-κB activation via the Notch-1 signaling pathway. In conclusion, our results suggest that inhibition of NF-κB activity via the Notch-1 pathway may be a novel mechanism by which Gen suppresses the growth of triple-negative breast cancer cells. Further preclinical and clinical studies are warranted to further investigate the application of Gen for the treatment of triple-negative breast cancer.



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August 2012
Volume 30 Issue 2

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Pan, H., Zhou, W., He, W., Liu, X., Ding, Q., Ling, L. ... Wang, S. (2012). Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway. International Journal of Molecular Medicine, 30, 337-343.
Pan, H., Zhou, W., He, W., Liu, X., Ding, Q., Ling, L., Zha, X., Wang, S."Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway". International Journal of Molecular Medicine 30.2 (2012): 337-343.
Pan, H., Zhou, W., He, W., Liu, X., Ding, Q., Ling, L., Zha, X., Wang, S."Genistein inhibits MDA-MB-231 triple-negative breast cancer cell growth by inhibiting NF-κB activity via the Notch-1 pathway". International Journal of Molecular Medicine 30, no. 2 (2012): 337-343.