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

FEBS Letters

Ding, Yi¹  Sakai, Toshiyuki¹  Bai, Fulu¹  Matsui, Takayoshi¹  Matsukawa, Yoshizumi¹  Ohtani-Fujita, Naoko¹ 

[1] Department of Preventive Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602, Japan

关键词: Flavone;    A549 cell;    Growth inhibition;    Cell cycle;    p21/WAF1;    Promoter;    PBS;    phosphate buffered saline;    CDK;    cyclin dependent kinase;    DMEM;    Dulbecco's modified Eagle's medium;   

DOI  :  10.1016/S0014-5793(98)01198-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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 μM flavone causes cell cycle arrest at the G₁ 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 μM flavone significantly increases the promoter activity of the p21/WAF1 gene by 5-fold. These results suggest that the G₁ phase arrest by flavone is due to p53-independent transcriptional induction of the p21/WAF1 gene and the subsequent dephosphorylation of RB protein.

【 授权许可】

Unknown