title: Natural Bcl-2 inhibitor (-)- gossypol induces protective autophagy via reactive oxygen species-high mobility group box 1 pathway in Burkitt lymphoma.
abstract: (-)- 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 in vivo and in vitro 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 N-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.
authors: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University , Chongqing , China.
authors: Zhenhong
authors: Z
authors: Ni
authors: Xufang
authors: X
authors: Dai
authors: Bin
authors: B
authors: Wang
authors: Wen
authors: W
authors: Ding
authors: Panke
authors: P
authors: Cheng
authors: Liang
authors: L
authors: Xu
authors: Jiqin
authors: J
authors: Lian
authors: Fengtian
authors: F
authors: He
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D006072:Gossypol / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D021381:Protein Transport / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D024243:HMGB1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D006072:Gossypol