Anti-proliferative targets of sulforaphane in ovarian cancer

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Epidemiological studies have shown that an increased consumption of fruits and vegetables reduces the risk of ovarian cancer. However, the literature does not contain many reports on the use of dietary components as chemopreventive agents for ovarian cancer. Sulforaphane (SFN) is derived from the breakdown of glucoraphanin and is found in large amounts in cruciferous vegetables, particularly broccoli. We observed a strong anti-cancer effect of SFN on human ovarian cancer cell line SKOV3 by cell viability assays and determined the IC₅₀ to be 10 μM. The loss of viability was due to induction of apoptosis where we observed a four fold increase in apoptosis at 10 μM going upto 20 fold at 100 μM. The apoptotic effect that results in the loss of viability is preceded by a significant effect on the regulator of cell cycle transition molecules specifically cdk4. The steady state level of cdk4 decreased in dose dependent manner with complete abrogation at 20 μM. In an effort to identify further upstream targets of SFN we examined the effect of SFN on signal transduction pathways that may be of significance in ovarian cancer. We observed that both total Akt protein and the active phosphorylated levels of Akt were significantly inhibited in SFN treated SKOV3 cells. We conclude that the pro-survival Akt pathway is a target of the chemopreventive SFN that may lead to cell cycle inhibition and induction of apoptosis and propose use of SFN with other chemotherapeutic agents that target phosphorylation mediated signal transduction pathways in ovarian cancer.