Involvement of Proapoptotic Bcl-2 Family Proteins in Antifungal Agent Terbinafine-induced Mitochondr

来源 :BIT Life Sciences 1st Annual World Cancer Congess-2008(2008中 | 被引量 : 0次 | 上传用户:gdzsljw
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  Terbinafine (TB, lamisil®), a promising world widely used oral-antifungal agent, has been used in the treatment of superficial mycosis.In this study, we found that apoptosis but not cell growth arrest was induced by TB (1  M, for 24h) in human promyelocytic leukemia (HL60) cells.The apoptotic effect induced by TB in the HL60 cell was not through the general differentiation mechanisms evidenced by evaluation of three recognized markers, including CD1 1b, CD33, and morphological features.In addition, our results also revealed that TB-induced apoptosis was not through the cellular surface CD 95 receptor-mediated signaling pathway.We found that the mitochondria membrane in the TB-treated HL 60 cells was dissipated by decreasing of the electrochemical gradient (AΨm) led to leakage ofcytochrome c from mitochondria into cytosol.Such effects were completely blocked by in vitro transfection of the HL60 cells with Bcl-2 overexpression plasmid (HL60/Bcl-2).However, our data found that TB-mediated apoptosis could not be completely prevented in the Bcl-2 over expressed (HL60/Bcl-2) cells.Such results implied that additional mediators (such as caspase-9) other than mitochondria membrane permeability might contribute to the TB-induced cellular apoptosis signaling.This hypothesis was supported by the evidence that administration of caspases-9 specific inhibitor (z-LEHD-fmk) blocked the TB-induced apoptosis.Our studies highlight the molecular mechanisms ofTB-induced apoptosis in human promyelocytic leukemia (HL60) cells.
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