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

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 autop...

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Autores principales: Miao, Qing, Bi, Lin-Lin, Li, Xin, Miao, Shan, Zhang, Jin, Zhang, Song, Yang, Qian, Xie, Yan-Hua, Zhang, Jian, Wang, Si-Wang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565325/
https://www.ncbi.nlm.nih.gov/pubmed/23344047
http://dx.doi.org/10.3390/ijms14011370
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author Miao, Qing
Bi, Lin-Lin
Li, Xin
Miao, Shan
Zhang, Jin
Zhang, Song
Yang, Qian
Xie, Yan-Hua
Zhang, Jian
Wang, Si-Wang
author_facet Miao, Qing
Bi, Lin-Lin
Li, Xin
Miao, Shan
Zhang, Jin
Zhang, Song
Yang, Qian
Xie, Yan-Hua
Zhang, Jian
Wang, Si-Wang
author_sort Miao, Qing
collection PubMed
description 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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spelling pubmed-35653252013-03-13 Anticancer Effects of Bufalin on Human Hepatocellular Carcinoma HepG2 Cells: Roles of Apoptosis and Autophagy Miao, Qing Bi, Lin-Lin Li, Xin Miao, Shan Zhang, Jin Zhang, Song Yang, Qian Xie, Yan-Hua Zhang, Jian Wang, Si-Wang Int J Mol Sci Article 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. MDPI 2013-01-11 /pmc/articles/PMC3565325/ /pubmed/23344047 http://dx.doi.org/10.3390/ijms14011370 Text en © 2013 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Miao, Qing
Bi, Lin-Lin
Li, Xin
Miao, Shan
Zhang, Jin
Zhang, Song
Yang, Qian
Xie, Yan-Hua
Zhang, Jian
Wang, Si-Wang
Anticancer Effects of Bufalin on Human Hepatocellular Carcinoma HepG2 Cells: Roles of Apoptosis and Autophagy
title Anticancer Effects of Bufalin on Human Hepatocellular Carcinoma HepG2 Cells: Roles of Apoptosis and Autophagy
title_full Anticancer Effects of Bufalin on Human Hepatocellular Carcinoma HepG2 Cells: Roles of Apoptosis and Autophagy
title_fullStr Anticancer Effects of Bufalin on Human Hepatocellular Carcinoma HepG2 Cells: Roles of Apoptosis and Autophagy
title_full_unstemmed Anticancer Effects of Bufalin on Human Hepatocellular Carcinoma HepG2 Cells: Roles of Apoptosis and Autophagy
title_short Anticancer Effects of Bufalin on Human Hepatocellular Carcinoma HepG2 Cells: Roles of Apoptosis and Autophagy
title_sort anticancer effects of bufalin on human hepatocellular carcinoma hepg2 cells: roles of apoptosis and autophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565325/
https://www.ncbi.nlm.nih.gov/pubmed/23344047
http://dx.doi.org/10.3390/ijms14011370
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