Ovarian cancer (OvCar) has poor prognosis when it is detected in late stage. Epidemiological studies indicate decreased risk of OvCar with increased consumption of fruits and vegetables. Bioactive compounds such as diindolylmethane and sulforaphane that are constituents of cruciferous vegetables have been shown to have anti-cancer properties. We are studying the anti-cancer activity of sulforaphane in OvCar, which shows potent anti-proliferative effects on SKOV3 cells that leads to the induction of programmed cell death. We next investigated the effects of sulforaphane on Akt and MAP kinase signal transduction pathways, which are important pro-survival signaling pathways operating in OvCar, in order to define the molecular mechanism of the anti-proliferative effects. In SKOV3 cells treated with sulforaphane, we observed a downregulation in Akt, inhibition in pAkt levels and consequent loss of kinase activity. We also observed an upregulation in ERK levels along with upregulation of NFκB and p21cip/WAF1. Sulforaphane, thus downregulates Akt pathway and positively regulates p21 expression through ERK leading to inhibition in OvCar cell proliferation. We thus demonstrate a multi-targeted approach of sulforaphane in mediating anti-proliferative effects by differential modulation of two critical pro-survival signal transduction pathways to manifest its anti-cancer activity.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA