title: Casticin induces ovarian cancer cell apoptosis by repressing FoxM1 through the activation of FOXO3a.
abstract: Casticin, a polymethoxyflavone, is reported to have anticancer activities. The aim of the present study was to examine the molecular mechanisms by which casticin induces apoptosis in ovarian cancer cells. The human ovarian cancer cell lines SKOV3 and A2780 were culturedin vitro. Various molecular techniques, including histone/DNA enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction (RT-PCR), western blot analysis and gene transfection, were used to assess the expression of FOXO3a and forkhead box protein M1 (FoxM1) in casticin-treated ovarian cancer cell lines. Casticin-induced apoptotic cell death was accompanied by the activation of transcription factor FOXO3a, with a concomitant decrease in the expression levels of FoxM1 and its downstream target factors, namely survivin and polo-like kinase 1 (PLK1), and an increase in p27KIP1. A small inhibitory RNA (siRNA) knockout of FoxM1 potentiated casticin-induced apoptosis in ovarian cancer cells. Silencing FOXO3a expression using siRNA increased FoxM1 expression levels and clearly attenuated the induction of apoptosis by casticin treatment. These results show that casticin-induced apoptosis in ovarian cancer may be caused by the activation of FOXO3a, leading to FoxM1 inhibition.
authors.affiliation: Department of Gynaecology and Obstetrics, The People's Hospital of Hunan Province, First Affiliated Hospital of Hunan Normal University, Changsha 410005;
authors.forename: Ling
authors.initials: L
authors.lastname: Jiang
authors.forename: Xiao-Cheng
authors.initials: XC
authors.lastname: Cao
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Cao
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Quan
authors.forename: Xi-Feng
authors.initials: XF
authors.lastname: Sheng
authors.forename: Kai-Qun
authors.initials: KQ
authors.lastname: Ren
keywords: FOXO3a; apoptosis; casticin; forkhead box protein M1; ovarian cancer