Chalcone arrests cell cycle progression and induces apoptosis through induction of mitochondrial pathway and inhibition of nuclear factor kappa B signalling in human bladder cancer cells.
Chalcones (1,3-diphenyl-2-propenone) are cancer preventive food components found in a human diet rich in fruits and vegetables. In this study, we first report the chemopreventive effect of chalcone in two human bladder cancer cell lines: T24 and HT-1376. The results show that chalcone inhibits the proliferation of T24 and HT-1376 cells by inducing apoptosis and blocking cell cycle progression in the G2/M phase. Western blot assay showed that chalcone significantly increases the expression of p21 and p27 proteins, and decreases the levels of cyclin B1, cyclin A and Cdc2, thereby contributing to cell cycle arrest. In addition, chalcone increased the expression of Bax and Bak, but decreased the levels of Bcl-2 and Bcl-X(L) and subsequently triggered mitochondrial apoptotic pathway (release of cytochrome c and activation of caspase-9 and caspase-3). Our study suggests that the induction of mitochondrial pathway and inhibition of the nuclear factor kappa B survival system may play important roles in the antiproliferative activity of chalcone in T24 and HT-1376 cells.
Shen
Kun-Hung
KH
Cell Biology Laboratory, Department of Biotechnology, Chia Nan University of Pharmacy and Science, 60 Erh-Jen Road Sec. 1, Jen-Te, Tainan 717, Taiwan.
Chang
Jiunn-Kae
JK
Hsu
Ya-Ling
YL
Kuo
Po-Lin
PL
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000494:pharmacology*; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction; D001749:Urinary Bladder Neoplasms; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016588:Anticarcinogenic Agents; C534699:CCNB1 protein, human; D019925:Cyclin A; D019926:Cyclin B; D056744:Cyclin B1; D016328:NF-kappa B; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D002599:Chalcone; D016203:CDC2 Protein Kinase; D020169:Caspases