Natural Bcl-2 inhibitor (−)– gossypol induces protective autophagy via reactive oxygen species–high mobility group box 1 pathway in Burkitt lymphoma. Issue 10 (October 2013)

• Record Type: Journal Article
• Authors: Ni, Zhenhong; Dai, Xufang; Wang, Bin; Ding, Wen; Cheng, Panke; Xu, Liang; Lian, Jiqin; He, Fengtian
• Is Part Of: Leukemia & lymphoma. Volume 54:Issue 10(2013:Oct.)
• Page Start: 2263
• Page End: 2268
• Publication Date: 2013-10
• Subjects: Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2013.775437
• Languages: English
• ISSNs: 1042-8194

Abstract

<abstract> <title>Abstract</title> <p>(−)– Gossypol, a natural inhibitor of anti-apoptotic Bcl-2 proteins, has presented an effective anti-tumor activity in numerous preclinical trials. More and more evidence <italic>in vivo</italic> and <italic>in vitro</italic> validates that (−)– gossypol can dramatically suppress cell proliferation and induce cell death in hematological malignancies. However, the detailed mechanisms are not well known. In the present study, we showed that treatment with (−)– gossypol stimulated reactive oxygen species (ROS) generation and induced autophagy in Burkitt lymphoma cells. Antioxidant <italic>N</italic>-acetyl-cysteine (NAC) pretreatment attenuated (−)– gossypol-induced autophagy. Furthermore, (−)– gossypol treatment increased the translocation of high mobility group box 1 (HMGB1) from nuclei to cytoplasm, which can be suppressed by NAC pretreatment. NAC pretreatment also dramatically enhanced (−)– gossypol-induced apoptosis and total cell death. These results indicate that (−)– gossypol induces a protective autophagy in Burkitt lymphoma cells, partly due to ROS induction and cytosolic translocation of HMGB1. Antioxidants may serve as potent chemosensitizers to enhance cell death through blocking (−)– gossypol-induced autophagy.</p> </abstract>