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Sulforaphane Induces Cell Cycle Arrest, Migration, Invasion, and Apoptosis in Epithelial Ovarian Cancer Cells

Linus Chuang, Nimesh Nagarsheth, Monica Prasad Hayes, Konstantin Zakashansky, Herbert Gretz, III, Farr R. Nezhat, Xiaohua Wu, David Fishman, Jen-Wei Chiao

Abstract


Objectives: Isothiocyanates (ITC) has long been shown to demonstrate chemopreventive properties. Sulforaphane (SFN) is a major ITC present in broccoli and other cruciferous vegetables. We reviewed the current literatures of SFN on ovarian carcinoma cell lines.
Methods: Studies were conducted on the effects of SFN on the growth of the OVCAR-3, MDAH 2774 and SKOV-3 ovarian carcinoma cell lines. Chuang et al. evaluated the effect of SFN on ovarian cancer cell cycles. Subsequently Chaudhuri et al. determined the specific pathway that was affected and Bryant et al. explored the signaling mechanisms through which SFN influences the cell growth and proliferation in ovarian cancer cell lines.
Results: Chuang et al. showed a concentration dependent decrease in cell density. Analysis of cell cycle phase progression revealed a decrease in the cell populations in S and G2M phases, with an increase of G1 cell population, indicating a G1 cell cycle arrest. The degree of decrease in the replicating population was concentration and time dependent. These results clearly demonstrated an effect of SFN in inducing growth arrest and apoptosis in ovarian carcinoma cell lines. Chaudhuri et al. investigated the effects of sulforaphane on Akt signal transduction pathway. Both total Akt protein and active phosphorylated levels of Akt and phosphoinositide 3-kinase were significantly decreased in sulforaphane-treated ovarian cancer cell lines. Utilizing gene expression profile analysis, Bryant et al. showed SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex.
Conclusions: SFN induced growth arrest and cell death in ovarian cancer cells in G1 cell cycle arrest. The Akt pathway was identified as the possible target for SFN. SFN suppresses growth of ovarian cancer cells in vitro by modulating cell cycle regulatory proteins and by enhancing apoptosis. Inhibition of retinoblastoma (RB) phosphorylation and reduction in levels of free E2F-1 appear to play an important role in ovarian cancer growth arrest, migration, and invasion.

Keywords


Sulforaphane; apoptosis; epitheli al ovarian cancers; Placlitaxel

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References


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