Anticancer Effects of Bufalin on Human Hepatocellular Carcinoma HepG2 Cells: Roles of Apoptosis and Autophagy

作者：Miao, Qing; Bi, Lin-Lin; Li, Xin; Miao, Shan; Zhang, Jin; Zhang, Song; Yang, Qian; Xie, Yan-Hua; Zhang, Jian; Wang, Si-Wang

来源：International Journal of Molecular Sciences, 2013, 14(1): 1370-1382.

DOI：10.3390/ijms14011370

• hepatocellular carcinoma
• bufalin
• apoptosis
• autophagy
• AMPK
• mTOR

The traditional Chinese medicine bufalin, extracted from toad's skin, has been demonstrated to exert anticancer activities in various kinds of human cancers. The mechanisms of action lie in its capacity to induce apoptosis, or termed type I programmed cell death (PCD). However, type II PCD, or autophagy, participates in cancer proliferation, progression, and relapse, as well. Recent studies on autophagy seem to be controversial because of the dual roles of autophagy in cancer survival and death. In good agreement with previous studies, we found that 100 nM bufalin induced extensive HepG2 cell apoptosis. However, we also noticed bufalin triggered autophagy and enhanced Beclin-1 expression, LC3-I to LC3-II conversion, as well as decreased p62 expression and mTOR signaling activation in HepG2 cells. Blockage of autophagy by selective inhibitor 3-MA decreased apoptotic ratio in bufalin-treated HepG2 cells, suggesting a proapoptotic role of bufalin-induced autophagy. Furthermore, we investigated the underlying mechanisms of bufalin-induced autophagy. Bufalin treatment dose-dependently promoted AMPK phosphorylation while AMPK inhibition by compound C significantly attenuated bufalin-induced autophagy. Taken together, we report for the first time that bufalin induces HepG2 cells PCD, especially for autophagy, and the mechanism of action is, at least in part, AMPK-mTOR dependent.

• 出版日期2013-1
• 单位中国人民解放军总医院; 第四军医大学; 中国人民解放军空军军医大学; 中国人民解放军第四〇一医院