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.
MeSH terms
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Apoptosis / drug effects*
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Apoptosis / physiology
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CDC2 Protein Kinase / biosynthesis
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Calcium / metabolism*
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Capsicum*
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Caspase 3
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Caspases / metabolism*
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Cyclin D3
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Cyclin E / antagonists & inhibitors
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Cyclin E / biosynthesis
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Cyclin-Dependent Kinase 2 / biosynthesis
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Cyclins / biosynthesis
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Cytochromes c / biosynthesis
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Enzyme Activation
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G1 Phase / drug effects
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G1 Phase / physiology
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HL-60 Cells
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Humans
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Membrane Potentials / drug effects
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Mitochondrial Membranes / physiology
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Reactive Oxygen Species / metabolism
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Resting Phase, Cell Cycle / drug effects
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Resting Phase, Cell Cycle / physiology
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bcl-2-Associated X Protein / biosynthesis
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bcl-2-Associated X Protein / metabolism*
Substances
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BAX protein, human
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CCND3 protein, human
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Cyclin D3
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Cyclin E
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Cyclins
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Proto-Oncogene Proteins c-bcl-2
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Reactive Oxygen Species
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bcl-2-Associated X Protein
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Egtazic Acid
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Cytochromes c
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CDC2 Protein Kinase
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CDK2 protein, human
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Cyclin-Dependent Kinase 2
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CASP3 protein, human
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Caspase 3
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Caspases
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1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
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Calcium