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.