PROMOTER ACTIVATION AND FOLLOWING INDUCTION OF THE P21 WAF1 GENE BY FLAVONE IS INVOLVED IN G(1) PHASE ARREST IN A549 LUNG ADENOCARCINOMA CELLS/

Flavonoids are present in many plants including edible fruits and vege tables, Recently, many of the biological activities of flavonoids have been elucidated. Flavone is a well known flavonoid, and many of its d erivatives have been shown to have anti-proliferative effects on sever al cancer cells, We report here that flavone can effectively inhibit t he cell growth of human lung adenocarcinoma A549 cells in a dose-depen dent manner, and 100 mu M flavone causes cell cycle arrest at the G(1) phase, As a mechanism underlying the cell cycle arrest, flavone marke dly increases the mRNA and protein levels of a universal inhibitor of cyclin-dependent kinase, p21/WAF1, and inhibits phosphorylation of ret inoblastoma (RB) protein. Although A549 cells possess wild-type p53, f lavone does not induce the p53 protein, suggesting that p21/WAF1 induc tion is p53-independent, In addition, 100 mu M flavone significantly i ncreases the promoter activity of the p21/WAF1 gene by 5-fold, These r esults suggest that the G(1) phase arrest by flavone is due to p53-ind ependent transcriptional induction of the p21/WAF1 gene and the subseq uent dephosphorylation of RE protein. (C) 1998 Federation of European Biochemical Societies.