Tricetin, a dietary flavonoid, inhibits proliferation of human breast adenocarcinoma mcf-7 cells by blocking cell cycle progression and inducing apoptosis.
This study is the first to investigate the anticancer effect of tricetin in human breast adenocarcinoma MCF-7 cells. Results reveal that tricetin inhibits MCF-7 cells by blocking cell cycle progression in the G2/M phase and inducing apoptosis. Cell cycle blockade is associated with increased activation of ataxia telangiectasia-mutated (ATM). Activation of ATM by tricetin phosphorylated p53 at serine 15, resulting in increased stability of p53 by decreasing p53 and murine double minute-2 (MDM2) interaction. In addition, tricetin-mediated G2/M phase arrest was also associated with decreases in the amounts of cyclin B, cyclin A, cdc2 and cdc25C, and increases in the phosphorylation of Chk2, cdc25C and cdc2. The specific ATM inhibitor caffeine significantly decreased tricetin-mediated G2/M arrest by inhibiting the phosphorylation of p53 (serine 15) and Chk2. Tricetin-induced apoptotic cell death is associated with changes in the expression of Bax and Bak, decreasing levels of Bcl-2 and Bcl-X(L), and subsequently triggering the mitochondrial apoptotic pathway. In addition, pretreatment of cells with caspase-9 inhibitor blocked tricetin-induced apoptosis, indicating that caspase-9 activation is involved in tricetin-mediated MCF-7 cell apoptosis. These findings suggest that tricetin may be a promising chemopreventive agent against human breast cancer.
Hsu
Ya-Ling
YL
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Uen
Yih-Huei
YH
Chen
Yi
Y
Liang
Hsin-Lin
HL
Kuo
Po-Lin
PL
D000230:Adenocarcinoma / Q000473:pathology; D016588:Anticarcinogenic Agents; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling
D016588:Anticarcinogenic Agents; D061945:Caspase Inhibitors; D002867:Chromones; C469689:tricetin; D053453:Caspase 9