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Research Articles: Therapeutics, Targets, and Development

Antiproliferative activity of sulforaphane in Akt-overexpressing ovarian cancer cells

¹ Department of Microbiology and Immunology, New York Medical College, Valhalla, New York and ² Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Requests for reprints: Badithe T. Ashok, Department of Microbiology and Immunology, New York Medical College, Room 331, Basic Sciences Building, Grasslands Reservation, Valhalla, NY 10595. Phone: 914-594-4186; Fax: 914-594-4176. E-mail: ashok_badithe{at}nymc.edu

Abstract

Epidemiologic studies show a correlation between increased consumption of fruits and vegetables with reduced risk of ovarian cancer. One major bioactive compound found in cruciferous vegetables, particularly broccoli, is sulforaphane, derived from the breakdown of glucoraphanin. We observed potent antiproliferative effects of sulforaphane on human ovarian cancer cell line SKOV3 (IC₅₀ 40 µmol/L) and mouse ovarian cancer cell lines C3 and T3 (IC₅₀ 25 µmol/L each) by cell viability assays. The loss of viability is reflected by a down-regulation of cell cycle transition regulators cyclin D1, cyclin-dependent kinase 4 (cdk4), and cdk6. The upstream mediators of sulforaphane effects on the cell cycle in ovarian cancer are still unknown. However, because the Akt signal transduction pathway is overactivated in ovarian cancer, we investigated the effects of sulforaphane on this prosurvival pathway. Both total Akt protein and active phosphorylated levels of Akt (Ser⁴⁷³) and phosphoinositide 3-kinase were significantly decreased in sulforaphane-treated SKOV3, C3, and T3 cells with a concomitant inhibition of Akt kinase activity by sulforaphane in SKOV3 and C3 cells. This inhibitory effect of sulforaphane leads to a potent induction of apoptosis in all three cell lines, along with the cleavage of poly(ADP)ribose polymerase. Our study is the first to report the antiproliferative effects of sulforaphane in ovarian cancer and identifying the Akt pathway as a target of sulforaphane, with implications for the inhibition of carcinogenesis by diet-based chemoprevention. [Mol Cancer Ther 2007;6(1):334–45]

Grant support: National Cancer Institute research grants CA29502 (B.T. Ashok) and RO1CA103924 (S. Orsulic).

Received 7/12/06; revised 11/10/06; accepted 11/22/06.