TY - JOUR AB - Casticin, a polymethoxyflavone, has been reported to exert anticancer activities. The objectives of this study were to examine the molecular mechanisms by which casticin induces the growth inhibition and cell cycle arrest in human hepatocellular carcinoma (HCC) cells. The HCC cell lines Hep G2 and PLC/PRF/5 were cultured in vitro. The growth inhibitory effects of casticin were evaluated using clonogenic assays. The distribution of phases in the cell cycle was analyzed using flow cytometry (FCM) analysis with propidium iodide (PI) staining. Multiple molecular techniques, such as western blotting and gene transfection, were used to explore the molecular mechanisms of action. Our data demonstrated that casticin significantly inhibited cell viability and colony formation in HCC cells. Furthermore, it induced cell cycle arrest in the G2/M phase. Casticin inhibited phosphorylation of the FOXO3a protein and decreased the expression of FoxM1 and its downstream genes, such as cyclin-dependent kinase (CDK1), cdc25B and cyclin B and increased the expression of p27KIP1. Silencing of FOXO3a expression by small interfering RNA (siRNA) transfection clearly attenuated the inhibitory effects of casticin on FOXM1 expression and cell growth. Our findings provided clear evidence that casticin induces growth suppression and cell cycle arrest through inhibition of FOXO3a phosphorylation causing inactivation of FOXM1 in HCC cells. AD - Medical College, Hunan Normal University, Changsha 410013, P.R. China AU - He,Lihua AU - Yang,Xiaohong AU - Cao,Xiaocheng AU - Liu,Fei AU - Quan,Meifang AU - Cao,Jianguo DA - 2013/01/01 DO - 10.3892/or.2012.2076 EP - 108 IS - 1 JO - Oncol Rep KW - hepatocellular carcinoma casticin FOXO3a FOXM1 PY - 2013 SN - 1021-335X 1791-2431 SP - 103 ST - Casticin induces growth suppression and cell cycle arrest through activation of FOXO3a in hepatocellular carcinoma T2 - Oncology Reports TI - Casticin induces growth suppression and cell cycle arrest through activation of FOXO3a in hepatocellular carcinoma UR - https://doi.org/10.3892/or.2012.2076 VL - 29 ER -