title: 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.
authors.affiliation: Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan, ROC.
authors.forename: Mei-Fen
authors.initials: MF
authors.lastname: Tsou
authors.forename: Hsu-Feng
authors.initials: HF
authors.lastname: Lu
authors.forename: Ssu-Ching
authors.initials: SC
authors.lastname: Chen
authors.forename: Lii-Tzu
authors.initials: LT
authors.lastname: Wu
authors.forename: Yi-Shuan
authors.initials: YS
authors.lastname: Chen
authors.forename: Hsiu-Maan
authors.initials: HM
authors.lastname: Kuo
authors.forename: Song-Shei
authors.initials: SS
authors.lastname: Lin
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016203:CDC2 Protein Kinase / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism*; D002212:Capsicum; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D056743:Cyclin D3; D019927:Cyclin E / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis; D016213:Cyclins / Q000096:biosynthesis; D045304:Cytochromes c / Q000096:biosynthesis; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; C534696:CCND3 protein, human; D056743:Cyclin D3; D019927:Cyclin E; D016213:Cyclins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D004533:Egtazic Acid; D045304:Cytochromes c; D016203:CDC2 Protein Kinase; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium