Promoter activation and following induction of the p21/WAF1 gene by flavone is involved in G1 phase arrest in A549 lung adenocarcinoma cells

被引:44
作者
Bai, FL [1 ]
Matsui, T [1 ]
Ohtani-Fujita, N [1 ]
Matsukawa, Y [1 ]
Ding, Y [1 ]
Sakai, T [1 ]
机构
[1] Kyoto Prefectural Univ Med, Dept Prevent Med, Kamigyo Ku, Kyoto 602, Japan
关键词
flavone; A549; cell; growth inhibition; cell cycle; p21/WAF1; promoter;
D O I
10.1016/S0014-5793(98)01198-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Flavonoids are present in many plants including edible fruits and vegetables, Recently, many of the biological activities of flavonoids have been elucidated. Flavone is a well known flavonoid, and many of its derivatives have been shown to have anti-proliferative effects on several cancer cells, We report here that flavone can effectively inhibit the cell growth of human lung adenocarcinoma A549 cells in a dose-dependent manner, and 100 mu M flavone causes cell cycle arrest at the G(1) phase, As a mechanism underlying the cell cycle arrest, flavone markedly increases the mRNA and protein levels of a universal inhibitor of cyclin-dependent kinase, p21/WAF1, and inhibits phosphorylation of retinoblastoma (RB) protein. Although A549 cells possess wild-type p53, flavone does not induce the p53 protein, suggesting that p21/WAF1 induction is p53-independent, In addition, 100 mu M flavone significantly increases the promoter activity of the p21/WAF1 gene by 5-fold, These results suggest that the G(1) phase arrest by flavone is due to p53-independent transcriptional induction of the p21/WAF1 gene and the subsequent dephosphorylation of RE protein. (C) 1998 Federation of European Biochemical Societies.
引用
收藏
页码:61 / 64
页数:4
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