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Research Article

Gossypol induced apoptosis of polymorphonuclear leukocytes and monocytes: Involvement of mitochondrial pathway and reactive oxygen species

, , , , , , , , , & show all
Pages 320-330 | Received 22 Sep 2008, Accepted 02 Jan 2009, Published online: 01 Jun 2009
 

Abstract

The aim of this study was to determine how gossypol affects the viability and activity of polymorphonuclear leukocytes and monocytes in blood obtained from healthy donors. Loss of mitochondrial membrane potential (δψm) and apoptosis was maximized in human polymorphonuclear leukocytes and monocytes after incubation with gossypol. Pretreatment with a caspase-9 inhibitor or antioxidants (superoxide dismutase or Trolox) inhibited gossypol-induced loss of the δψm and apoptosis. Likewise, we observed participation of caspase -3, -7, and -10 in gossypol-induced apoptosis. Expression of the proapoptotic genes bax, bak, bad and p53/Tp53 increased in polymorphonuclear leukocytes exposed to gossypol. The expression of the anti-apoptotic genes bcl-XL and mcl-1 was reduced when polymorphonuclear leukocytes and monocytes were treated with gossypol. Gossypol treatment also inhibited yeast phagocytosis by these cells. We concluded that gossypol induces apoptosis in phagocytic cells and that this effect was dose-dependent. The findings in this report may be important to consider in light of possible gossypol use in clinical strategies for cancer treatment.

Acknowledgments

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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