Antiproliferative Effects (Cruciferous Vegs) Ova Ca

Antiproliferative effects of phenethyl isothiocyanate Against human ovarian cancer cells via inhibition of epidermal growth factor receptor

Sivakumar Loganathan, Ian Humphreys, Sanjay K. Srivastava. University of Pittsburgh Cancer Institute, Pittsburgh, PA and University of Pittsburgh, Pittsburgh, PA.

Ovarian cancer is on of the leading cause of gynecologic cancer-related deaths among women of all ages in the United States. The cause of ovarian cancer is not clear and is often detected at an advanced stage. The overall prognosis of ovarian cancer is very poor despite significant advances in surgical and therapeutic management.

Genetic alterations including overexpression of epidermal growth factor receptor (EGFR) (~70% of ovarian tumors) may play a crucial role in the proliferation and cell survival of these cancer cells. Several recent epidemiological studies have clearly suggested that higher consumption of cruciferous vegetables reduces the risk of ovarian cancer.

Our present studies demonstrate that phenethyl isothiocyanate (PEITC), a constituent of cruciferous vegetables such as broccoli, significantly inhibits the proliferation of NIH-OVCAR human ovarian cancer cells in culture with an IC50 of about 20 ýM (concentration that may be achieved clinically through dietary intake of cruciferous vegetables) and induces apoptosis in these cells.

Exposure of NIH-OVCAR cells to PEITC for 24h resulted in significant inhibition of the protein expression of EGFR as well as the phosphorylation of Akt at serine 473 in a dose-dependent manner. In addition, PEITC treatment also causes significant down-regulation of the anti-apoptotic protein Bcl-2.

Furthermore, apoptosis induced by PEITC in these cells was associated with significant cleavage of caspase-3 and PARP. Taken together, our results demonstrate for the first time that PEITC exerts antiproliferative activity against human ovarian cancer cells by targeting the EGFR pathway.

Based on our findings, it is logical to speculate that PEITC will find its place as novel dietary agent for the prevention and/or treatment of ovarian cancer.

[Supported in part by RO1 grant CA 106953 (to S.K.S.) awarded by the National Cancer Institute].

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