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Promoter activation and following induction of the p21/WAF1 gene by flavone is involved in G 1 phase arrest in A549 lung adenocarcinoma cells
Author(s) -
Bai Fulu,
Matsui Takayoshi,
Ohtani-Fujita Naoko,
Matsukawa Yoshizumi,
Ding Yi,
Sakai Toshiyuki
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01198-3
Subject(s) - retinoblastoma protein , cell cycle , a549 cell , cell cycle checkpoint , dephosphorylation , flavones , phosphorylation , chemistry , retinoblastoma , gene , kinase , cancer research , cell growth , biology , microbiology and biotechnology , biochemistry , cell , genetics , phosphatase
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 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 μM 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 RB protein.