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

International Journal of Molecular Sciences

Qing Miao³  Lin-Lin Bi³  Xin Li⁴  Shan Miao³  Jin Zhang⁵  Song Zhang¹  Qian Yang³  Yan-Hua Xie³  Jian Zhang² 

[1] Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi’an 710032, China; E-Mail:;Department of Pulmonary Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China;Institute of Materia Medica, Fourth Military Medical University, Xi’an 710032, China; E-Mails:;Department of Pharmacy, Chinese PLA General Hospital, Beijing 100850, China; E-Mail:;Department of Hand Surgery, 401 Military Hospital, Qingdao 266071, China; E-Mail:

关键词: hepatocellular carcinoma;    bufalin;    apoptosis;    autophagy;    AMPK;    mTOR;   

DOI  :  10.3390/ijms14011370

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.