Involvement of Bax, Bcl-2, Ca²⁺ and Caspase-3 in Capsaicin-induced Apoptosis of Human Leukemia HL-60 Cells

Abstract

The role of Ca²⁺ on the effects of capsaicin on human leukemia HL-60 cells in vitro and the molecular mechanisms of capsaicin-induced apoptosis were investigated. The flow cytometric analysis indicated that capsaicin decreased the percentage of viable HL-60 cells, via the induction of G₀/G₁-phase cell cycle arrest and apoptosis. Capsaicin-induced G₀/G₁-phase arrest involved the suppression of CDK2 and the cyclin E complex, which are check-point enzymes for cells moving from G₀/G₁- to S-phase. Capsaicin-induced apoptosis was associated with the elevation of intracellular reactive oxygen species and Ca²⁺ production, decreased the levels of mitochondrial membrane potential, promoted cytochrome c release and increased the activation of caspase-3. An intracellular Ca²⁺ chelator (BAPTA) significantly inhibited capsaicin-induced apoptosis. Capsaicin-induced apoptosis was time-and dose-dependent. These results suggest that the capsaicin-induced apoptosis of HL-60 cells may result from the activation of caspase-3 and the intracellular Ca²⁺ release pathway.