Molecular mechanism of matrine-induced apoptosis in leukemia K562 cells.
Matrine, a low toxic alkaloid purified from the Chinese herb Kushen, has been reported to induce apoptosis in leukemia K562 cells. In this study, the mechanism underling this apoptotic event was investigated. Treatment of K562 cells with matrine resulted in inhibition of cell survival more significantly than treatment of non-cancer fibroblast NIH3T3 cells. When K562 cells were incubated with matrine in higher than 0.2 mg/ml doses for 48 hours, the apoptotic cells were increased and both poly (ADP-ribose) polymerase (PARP) and caspase-3 were cleaved in a dose dependent manner. General caspase inhibitor (z-VAD-fmk) or caspase-3 inhibitor (z-DEVD-fmk) almost completely suppressed matrine-induced apoptosis. In addition, matrine increased proapoptotic protein bax and caused the release of cytochrome C. Taken together, the results suggest that matrine induces a cytochrome C-mediated, caspase-dependent apoptosis.
Liu
Xiao-Shan
XS
Center for Molecular Biology, School of Medicine, Shantou University, Shantou, Guangdong, 515031, China.
Jiang
Jikai
J
D000470:Alkaloids / Q000494:pharmacology*; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020014:K562 Cells; D009842:Oligopeptides / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011807:Quinolizines / Q000494:pharmacology*; D000093842:Matrines
D000470:Alkaloids; D000590:Amino Acid Chloromethyl Ketones; D000972:Antineoplastic Agents, Phytogenic; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D011807:Quinolizines; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D000093842:Matrines