dc.contributor.author | Cheng, P. | |
dc.contributor.author | Ni, Zhenhong | |
dc.contributor.author | Dai, Xufang | |
dc.contributor.author | Wang, Bin | |
dc.contributor.author | Ding, W. | |
dc.contributor.author | Smith, Amber Rae | |
dc.contributor.author | Xu, Liang | |
dc.contributor.author | Wu, D. | |
dc.contributor.author | He, Fengtian | |
dc.contributor.author | Lian, Jiqin | |
dc.date.accessioned | 2014-04-08T14:44:36Z | |
dc.date.available | 2014-04-08T14:44:36Z | |
dc.date.issued | 2013-02-07 | |
dc.identifier.citation | Cheng, P; Ni, Z; Dai, X; Wang, B; Ding, W; Smith, A Rae; Xu, L; Wu, D; He, F; & Lian, J; 2013 “The novel BH-3 mimetic apogossypolone induces Beclin-1- and ROS-mediated autophagy in human hepatocellular carcinoma cells” Cell Death and Disease. 4, e489 http://dx.doi.org/10.1038/cddis.2013.17 | |
dc.identifier.uri | http://hdl.handle.net/1808/13418 | |
dc.description.abstract | Apogossypolone (ApoG2), a novel derivative of gossypol, exhibits superior antitumor activity in Bcl-2 transgenic mice, and induces autophagy in several cancer cells. However, the detailed mechanisms are not well known. In the present study, we showed that ApoG2 induced autophagy through Beclin-1- and reactive oxygen species (ROS)-dependent manners in human hepatocellular carcinoma (HCC) cells. Incubating the HCC cell with ApoG2 abrogated the interaction of Beclin-1 and Bcl-2/xL, stimulated ROS generation, increased phosphorylation of ERK and JNK, and HMGB1 translocation from the nucleus to cytoplasm while suppressing mTOR. Moreover, inhibition of the ROS-mediated autophagy by antioxidant N-acetyl-cysteine (NAC) potentiates ApoG2-induced apoptosis and cell killing. Our results show that ApoG2 induced protective autophagy in HCC cells, partly due to ROS generation, suggesting that antioxidant may serve as a potential chemosensitizer to enhance cancer cell death through blocking ApoG2-stimulated autophagy. Our novel insights may facilitate the rational design of clinical trials for Bcl-2-targeted cancer therapy. | |
dc.description.sponsorship | Grant support: This study was supported in part by Chongqing Natural Science Foundation (CSTC, 2011BB5030), and by the Scientific Funds of Third Military Medical University (2011XHG02). | |
dc.publisher | Nature Publishing Group | |
dc.rights | This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/. | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/ | |
dc.subject | ApoG2 | |
dc.subject | ROS | |
dc.subject | Autophagy | |
dc.subject | HCC | |
dc.title | The novel BH-3 mimetic apogossypolone induces
Beclin-1- and ROS-mediated autophagy in human
hepatocellular carcinoma cells | |
dc.type | Article | |
kusw.kuauthor | Liang, Xu | |
kusw.kudepartment | Department of Molecular Biology | |
kusw.oastatus | fullparticipation | |
dc.identifier.doi | 10.1038/cddis.2013.17 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item meets KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess | |