Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 428, Issue 2, Pages 179-187Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2004.06.007
Keywords
gossypol; apoptosis; HL-60 cell; caspase; mitochondria; cytochrome C; reactive oxygen species
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Gossypol is a component present in cottonseeds and has been demonstrated to be an effective contraceptive drug in preventing spermatogenesis in mammalian species. In the present, we reported that gossypol could induce apoptosis in human promyelocytic leukemia cells (HL-60), as characterized by DNA fragmentation, poly(ADP) ribose polymerase (PARP) cleavage. The efficacious induction of apoptosis was observed at 50 muM for 6 h. Further molecular analysis showed that gossypol induced the truncation of Bid protein, the loss of mitochondrial membrane potential (DeltaPsi(m)), cytochrome c release from mitochondria into cytosol, and activation of caspase-3, -8, and -9. However, gossypol did not increase the level of reactive oxygen species (ROS), and antioxidants including N-acetyl cysteine (NAC) and catalase could not block gossypol-induced apoptosis in the HL-60 cells. These data suggest that gossypol induces apoptosis in HL-60 cells through ROS-independent mitochondrial dysfunction pathway. (C) 2004 Elsevier Inc. All rights reserved.
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