Involvement of proapoptotic Bcl-2 family members in terbinafine-induced mitochondrial dysfunction and apoptosis in HL60 cells

Kuo Ching Yang, Chi Chen Wu, Chih Hsiung Wu, Jur Hao Chen, Chien Hwa Chu, Chien Ho Chen, Yean Hwei Chou, Ying Jan Wang, Wen Sen Lee, How Tseng, Shyr Yi Lin, Chia Hwa Lee, Yuan Soon Ho

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8 Citations (Scopus)

Abstract

Terbinafine (TB, lamisil®), a promising world widely used oral-anti-fungal 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 μM, for 24 h) 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 CD11b, 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 HL60 cells was dissipated by decreasing of the electrochemical gradient (ΔΨm) led to leakage of cytochrome 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 of TB-induced apoptosis in human promyelocytic leukemia (HL60) cells.

Original languageEnglish
Pages (from-to)214-226
Number of pages13
JournalFood and Chemical Toxicology
Volume44
Issue number2
DOIs
Publication statusPublished - 2006 Feb 1

All Science Journal Classification (ASJC) codes

  • Food Science
  • Toxicology

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