期刊
TOXICOLOGY IN VITRO
卷 23, 期 5, 页码 874-879出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2009.05.001
关键词
Flavan; G2/M arrest; Apoptosis; Death receptor; Mitochondria
类别
2(+/-)-7,8,3',4',5'-pentamethoxyflavan (PMF), a synthetic flavan racemate, showed growth inhibitory effect on various kinds of tumor cells. The present study is to investigate the molecular mechanisms of action of PMF in human leukemia HL60 cells. Anti-proliferative effect of PMF on HL60 cells was associated with G2/M cell cycle arrest. which was mediated by regulating the expression of Cdc25C, cyclin A and p21 proteins and inhibiting the phosphorylation of Cdc2 at Thr161. PMF also induced apoptosis of HL60 cells via death receptor and mitochondria apoptotic pathways, which was characterized by DNA fragmentation, cleavage of poly (ADP-ribose) polymerase, caspase-3, caspase-8 and caspase-9, changes of Bcl-2 and Bax expression, cytochrome c release from mitochondria and a decrease in the mitochondrial membrane potential (MMP). These data suggest that PMF produces anti-tumor effect via induction of G2/M cell cycle arrest and apoptosis. (C) 2009 Elsevier Ltd. All rights reserved.
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