Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprouts and broccoli, is considered particularly promising as a chemo−preventive agent against cancer because it induces apoptosis and cell−cycle arrest in a variety of tumor types. Molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC.

SFN at concentrations of 5 − 20 micro M induced a dose−dependent suppression of growth in both cell lines with IC50 of around ~8 micro M over 3 day period with additive effects in conjunction with paclitaxel. SFN at ~8 micro M decreased growth by 40% and 20% on day 1 in 2774 and SkOV−3 respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration, exhibited progressively increased apoptotic cell death with increase in Bak/Bcl−2 ratio, cleavage of procaspase−9 and poly (ADP−ribose)−polymerase (PARP). Gene expression profile analysis of cell cycle regulated proteins revealed increased levels of tumor suppressor retinoblastoma protein (RB) and simultaneous decrease in the levels of E2F−1 transcription factor. SFN caused G1 cell cycle arrest by down modulation of phosphorylation of RB and by protecting RB−E2F−1 complex.

SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB) phosphorylation and reducing the levels of free E2F−1 appears to play an important role in EOC growth arrest.

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