Anemoside B4 exerts anti-cancer effect by inducing apoptosis and autophagy through inhibiton of PI3K/Akt/mTOR pathway in hepatocellular carcinoma

白头翁皂苷 B4 通过抑制肝细胞癌中的 PI3K/Akt/mTOR 通路诱导细胞凋亡和自噬发挥抗癌作用

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作者:Shuyi Xue, Yu Zhou, Jin Zhang, Zhuo Xiang, Yang Liu, Ting Miao, Guoxin Liu, Bangguo Liu, Xu Liu, Lixia Shen, Zhe Zhang, Mingchun Li, Qing Miao

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and novel therapeutic approaches are urgently required. Anemoside B4 (AB4) is a compound extracted from Pulsatilla chinensis (P. chinensis). Previous studies have indicated that P. chinensis extract P. chinensis saponins has anti-cancer activity. However, the pharmacological effect of AB4 in cancer is largely unknown. In this study, we investigated the anti-cancer efficacy of AB4 in HCC. We used CCK-8 assay and colony formation assay to evaluate the cytotoxicity of AB4 and found that this agent markedly inhibited SMMC7721 cell proliferation. By using a panel of morphological and molecular experiments, we reported that AB4 induced HCC SMMC7721 cell apoptosis and autophagy. Notably, AB4 treatment acts on the Bcl-2-caspase-3 pathway and Beclin-1-LC3-p62 pathway, thereby regulates both apoptosis and autophagy. Finally, we showed that AB4-induced apoptosis and autophagy converges at the PI3K/Akt/mTOR signaling. AB4 treatment inhibits this signaling transduction pathway and leads to HCC cell death. Collectively, our study highlighted the anti-cancer efficacy of AB4 and suggested that AB4 might be a novel way to treat HCC.

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