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.

Keywords::

• (−) –Gossypol
• ROS
• HMGB1
• autophagy

Acknowledgements

This study was supported in part by a grant from the Chongqing Natural Science Foundation (CSTC, 2011BB5030), and by Scientific Funds of the Third Military Medical University (2011XHG02).

Potential conflict of interest

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