Abstract Title:

Synergistic cytotoxic effect of genistein and doxorubicin on drug-resistant human breast cancer MCF-7/Adr cells.

Abstract Source:

Oncol Rep. 2014 Oct ;32(4):1647-53. Epub 2014 Jul 29. PMID: 25109508

Abstract Author(s):

Jia-Peng Xue, Geng Wang, Zong-Bin Zhao, Qun Wang, Yun Shi

Article Affiliation:

Jia-Peng Xue


The molecular mechanisms underlying genistein-mediated reversal of chemoresistance remains unknown. In the present study, we investigated the molecular mechanisms by which genistein overcomes chemoresistance and its effect on doxorubicin-induced cytotoxicity. Consistent with previous reports, genistein combined with doxorubicin had a synergistic effect on MCF-7/Adr cells, and genistein reduced the chemoresistance of these cells. Genistein treatment increased the intracellular accumulation of doxorubicin but did not influence P-gp function. The combination of genistein and doxorubicin significantly induced cell cycle arrest and apoptosis. Genistein treatment strongly inhibited HER2/neu but not MDR-1 expression at both the mRNA and protein levels. Therefore, our results demonstrated that genistein combined with doxorubicin had a synergistic effect on MCF-7/Adr cells, and the mechanisms likely involve an increase in the intracellular accumulation of doxorubicin and suppression of HER2/neu expression.

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