ERβ up-regulation was involved in silibinin-induced growth inhibition of human breast cancer MCF-7 cells

作者：Zheng, Nan; Liu, Lu; Liu, Weiwei; Zhang, Ping; Huang, Huai; Zang, Linghe; Hayashi, Toshihiko; Tashiro, Shin-ichi; Onodera, Satoshi; Xia, Mingyu^*; Ikejima, Takashi^*

来源：Archives of Biochemistry and Biophysics, 2016, 591: 141-149.

DOI：10.1016/j.abb.2016.01.002

• Silibinin
• Estrogen receptor beta (ER beta)
• ER-beta antagonist (PHTPP)
• ER-beta agonist (DPN)
• Apoptosis
• Autophagy

We previously reported that silibinin induced a loss of cell viability in breast cancer (MCF-7) cells by ER alpha down-regulation. But whether this cytotoxicity depends on another estrogen receptor, ER beta, has yet to be elucidated. Therefore, we sought to explore the effects of ER beta modulation on cell viability by using an ER beta-selective agonist (Diarylprepionitrile, DPN) and an antagonist (PHTPP). Our data demonstrated that ER beta served as a growth suppressor in MCF-7 cells, and the incubation of silibinin, elevated ER beta expression, resulting in the tumor growth inhibition. The cytotoxic effect of silibinin was diminished by PHTPP and enhanced by DPN. Silencing of ER beta by siRNA confirmed these results. Apoptotic cascades, including the sequential activation of caspase-9 and-6, and finally the cleavage of caspase substrates, PARP and ICAD, caused by treatment with silibinin, were all repressed by PHTPP pre-treatment but exacerbated by DPN. Unlike ER alpha, ER beta did not involve autophagic process in the regulation, since neither autophagic inhibitor (3-MA) nor the inducer (rapamycin) affected the cell survival rates regardless ER beta activity. Taken together, silibinin induced apoptosis through mitochondria) pathway by up-regulating ER beta pathways in MCF-7 cells without the involvement of autophagy.

• 出版日期2016-2-1
• 单位沈阳药科大学; 河北医科大学