Anticancer effects of bufalin on human hepatocellular carcinoma HepG2 cells: roles of apoptosis and autophagy.
Anticancer effects of bufalin on human hepatocellular carcinoma HepG2 cells: roles of apoptosis and autophagy.
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DOI：
10.3390/ijms14011370
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发表时间：
2013-01-11
影响因子：
5.6
通讯作者：
Wang SW
中科院分区：
文献类型：
--
作者：
Miao Q;Bi LL;Li X;Miao S;Zhang J;Zhang S;Yang Q;Xie YH;Zhang J;Wang SW
传统中药蟾毒灵是从蟾皮中提取的，已被证明对多种人类癌症具有抗癌活性。作用机制在于其诱导细胞凋亡或称为I型程序性细胞死亡（PCD）的能力。然而，II型PCD或自噬也参与癌症增殖、进展和复发。由于自噬在癌症生存和死亡中的双重作用，最近对自噬的研究似乎存在争议。与以前的研究一致，我们发现100 nM蟾蜍灵诱导广泛的HepG 2细胞凋亡。然而，我们也注意到蟾蜍灵在HepG 2细胞中触发自噬并增强Beclin-1表达，LC 3-I向LC 3-II转化，以及降低p62表达和mTOR信号激活。选择性抑制剂3-MA阻断自噬降低蟾蜍灵处理的HepG 2细胞的凋亡率，表明蟾蜍灵诱导的自噬具有促凋亡作用。此外，我们研究了蟾蜍灵诱导自噬的潜在机制。蟾毒灵处理剂量依赖性地促进AMPK磷酸化，而化合物C对AMPK的抑制显著减弱蟾毒灵诱导的自噬。综上所述，我们首次报道蟾蜍灵诱导HepG 2细胞PCD，特别是自噬，并且作用机制至少部分是AMPK-mTOR依赖性的。
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.
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影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
13.3
作者：
Liu, Yuan-Ling;Yang, Pei-Ming;Chen, Ching-Chow
通讯作者：
Chen, Ching-Chow
Bufadienolide 化合物通过抑制 STAT3/Mcl-1 通路使人乳腺癌细胞对 TRAIL 诱导的细胞凋亡敏感
影响因子：
7.2
作者：
Dong, Yinhui;Yin, Shutao;Hu, Hongbo
通讯作者：
Hu, Hongbo
影响因子：
9.3
作者：
Misirkic, Maja;Janjetovic, Kristina;Trajkovic, Vladimir
通讯作者：
Trajkovic, Vladimir
影响因子：
64.8
作者：
Kuma, A;Hatano, M;Mizushima, N
通讯作者：
Mizushima, N