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  • Title: ERα down-regulation plays a key role in silibinin-induced autophagy and apoptosis in human breast cancer MCF-7 cells.
    Author: Zheng N, Zhang P, Huang H, Liu W, Hayashi T, Zang L, Zhang Y, Liu L, Xia M, Tashiro S, Onodera S, Ikejima T.
    Journal: J Pharmacol Sci; 2015 Jul; 128(3):97-107. PubMed ID: 26117209.
    Abstract:
    The estrogen receptor alpha (ERα) has been proven to be one of the most important therapeutic targets in breast cancer over the last 30 years. Previous studies pointed out that a natural flavonoid, silibinin, induced apoptosis in human breast cancer MCF-7 cells. In the present study we report that exposure of MCF-7 cells to silibinin led to cell death through the down-regulation of ERα expression. Silibinin-induced apoptosis of MCF-7 cells through up-regulation of caspase 6 due to ERα signalling repression was further boosted by ERα antagonist. Moreover, up-regulation of autophagy induced by silibinin accounted for apoptotic exacerbation, being further enhanced by ERα inhibition. Upon ERα activation, series of downstream signalling pathways can be activated. We found that silibinin reduced the expressions of Akt/mTOR and extracellular-signal-related kinase (ERK), which respectively accounted for the induction of autophagy and apoptosis. These effects were further augmented by co-treatment with ERα inhibitor. We conclude that the treatment with silibinin of ERα-positive MCF-7 cells down-regulates the expression of ERα, and subsequently mTOR and ERK signaling pathways, ERα downstream, finally resulting in induction of autophagy and apoptosis.
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