Stachydrine hydrochloride inhibits proliferation and induces apoptosis of breast cancer cells via inhibition of Akt and ERK pathways

盐酸水苏碱通过抑制 Akt 和 ERK 通路抑制乳腺癌细胞增殖并诱导其凋亡

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作者:Ming Wang, Zhi-Jun Shu, Ying Wang, Wei Peng

Abstract

Although a series of efficient Akt and ERK inhibitors have been developed to target breast cancer cells, drug resistance can emerge after long-term treatment. Therefore, it is essential to uncover alternative drugs for inhibiting survival pathways in breast cancer cells. Stachydrine hydrochloride, a well-known bioactive ingredients extracted from HerbaLeonuri, has proven to be very efficient for the treatment of various diseases such as prostate cancer. However, whether stachydrine hydrochloride can exert similar prophylactic and therapeutic effects against breast cancer, and the probable underlying molecular mechanism remain unknown. In the present work, the effects of stachydrine hydrochloride on human breast cancer cell lines (T47D and MCF-7) were evaluated. Our results showed that Stachydrine hydrochloride inhibits cell proliferation and induces primary apoptosis and ROS production in T47D and MCF-7 cells in time- and dose-dependent manner. Mechanistically, Stachydrine hydrochloride treatment induced caspase-3 activation and decreased the expression of the anti-apoptotic protein Bcl-2. Moreimportantly, Stachydrine hydrochloride simultaneously inhibited the phosphorylation of Akt and ERK proteins. Overall, our data indicated that Stachydrine hydrochloride induces apoptosis in MCF-7 and T47D cells and exerts inhibitory effects on proliferation by concurrently suppressing Akt and ERK survival signals, suggesting its potential efficiency in treatment of breast cancer.

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