Casticin induces ovarian cancer cell apoptosis by repressing FoxM1 through the activation of FOXO3a

Jiang,Ling; Cao,Xiao-Cheng; Cao,Jian-Guo; Liu,Fei; Quan,Mei-Fang; Sheng,Xi-Feng; Ren,Kai-Qun

doi:10.3892/ol.2013.1258

Casticin induces ovarian cancer cell apoptosis by repressing FoxM1 through the activation of FOXO3a

Authors:
- Ling Jiang
- Xiao-Cheng Cao
- Jian-Guo Cao
- Fei Liu
- Mei-Fang Quan
- Xi-Feng Sheng
- Kai-Qun Ren
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Affiliations: Department of Gynaecology and Obstetrics, The People's Hospital of Hunan Province, First Affiliated Hospital of Hunan Normal University, Changsha 410005, P.R. China, Laboratory of Medicine Engineering, Medical College, Hunan Normal University, Changsha 410013, P.R. China
Published online on: March 14, 2013 https://doi.org/10.3892/ol.2013.1258
Pages: 1605-1610

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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 cultured in 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.

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