title: Promoter activation and following induction of the p21/WAF1 gene by flavone is involved in G1 phase arrest in A549 lung adenocarcinoma cells.
abstract: 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 microM 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 microM 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.
authors.affiliation: Department of Preventive Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Bai
authors.forename: T
authors.initials: T
authors.lastname: Matsui
authors.forename: N
authors.initials: N
authors.lastname: Ohtani-Fujita
authors.forename: Y
authors.initials: Y
authors.lastname: Matsukawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ding
authors.forename: T
authors.initials: T
authors.lastname: Sakai
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D047309:Flavones; D005419:Flavonoids; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C043562:flavone