1. Academic Validation
  2. The novel BH-3 mimetic apogossypolone induces Beclin-1- and ROS-mediated autophagy in human hepatocellular carcinoma [corrected] cells

The novel BH-3 mimetic apogossypolone induces Beclin-1- and ROS-mediated autophagy in human hepatocellular carcinoma [corrected] cells

  • Cell Death Dis. 2013 Feb 7;4(2):e489. doi: 10.1038/cddis.2013.17.
P Cheng 1 Z Ni X Dai B Wang W Ding A Rae Smith L Xu D Wu F He J Lian
Affiliations

Affiliation

  • 1 Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
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.

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