Genistein targets the cancerous inhibitor of PP2A to induce growth inhibition and apoptosis in breast cancer cells

  • Authors:
    • Qingxia Zhao
    • Ming Zhao
    • Amanda B. Parris
    • Ying Xing
    • Xiaohe Yang
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  • Published online on: June 30, 2016     https://doi.org/10.3892/ijo.2016.3588
  • Pages: 1203-1210
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Abstract

Genistein is a soy isoflavone with phytoestrogen and tyrosine kinase inhibitory properties. High intake of soy/genistein has been associated with reduced breast cancer risk. Despite the advances in genistein-mediated antitumor studies, the underlying mechanisms remain unclear. In the present study, we investigated genistein-induced regulation of the cancerous inhibitor of protein phosphatase 2A (CIP2A), a novel oncogene frequently overexpressed in breast cancer, and its functional impact on genistein-induced growth inhibition and apoptosis. We demonstrated that genistein induced downregulation of CIP2A in MCF-7-C3 and T47D breast cancer cells, which was correlated with its growth inhibition and apoptotic activities. Overexpression of CIP2A attenuated, whereas CIP2A knockdown sensitized, genistein-induced growth inhibition and apoptosis. We further showed that genistein-induced downregulation of CIP2A involved both transcriptional suppression and proteasomal degradation. In particular, genistein at higher concentrations induced concurrent downregulation of E2F1 and CIP2A. Overexpression of E2F1 attenuated genistein-induced downregulation of CIP2A mRNA, indicating the role of E2F1 in genistein-induced transcriptional suppression of CIP2A. Taken together, our results identified CIP2A as a functional target of genistein and demonstrated that modulation of E2F1-mediated transcriptional regulation of CIP2A contributes to its downregulation. These data advance our understanding of genistein-induced growth inhibition and apoptosis, and support further investigation on CIP2A as a therapeutic target of relevant anticancer agents.
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September 2016
Volume 49 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Zhao, Q., Zhao, M., Parris, A.B., Xing, Y., & Yang, X. (2016). Genistein targets the cancerous inhibitor of PP2A to induce growth inhibition and apoptosis in breast cancer cells. International Journal of Oncology, 49, 1203-1210. https://doi.org/10.3892/ijo.2016.3588
MLA
Zhao, Q., Zhao, M., Parris, A. B., Xing, Y., Yang, X."Genistein targets the cancerous inhibitor of PP2A to induce growth inhibition and apoptosis in breast cancer cells". International Journal of Oncology 49.3 (2016): 1203-1210.
Chicago
Zhao, Q., Zhao, M., Parris, A. B., Xing, Y., Yang, X."Genistein targets the cancerous inhibitor of PP2A to induce growth inhibition and apoptosis in breast cancer cells". International Journal of Oncology 49, no. 3 (2016): 1203-1210. https://doi.org/10.3892/ijo.2016.3588