TY - JOUR T1 - Gedunin, a Novel Natural Substance, Inhibits Ovarian Cancer Cell Proliferation JF - International Journal of Gynecologic Cancer JO - Int J Gynecol Cancer SP - 1564 LP - 1569 DO - 10.1111/IGC.0b013e3181a83135 VL - 19 IS - 9 AU - Siddharth G. Kamath AU - Ning Chen AU - Yin Xiong AU - Robert Wenham AU - Sachin Apte AU - Marcia Humphrey AU - Janiel Cragun AU - Johnathan M. Lancaster Y1 - 2009/11/01 UR - http://ijgc.bmj.com/content/19/9/1564.abstract N2 - The discovery of more active therapeutic compounds is essential if the outcome for patients with advanced-stage epithelial ovarian cancer is to be improved. Gedunin, an extract of the neem tree, has been used as a natural remedy for centuries in Asia. Recently, gedunin has been shown to have potential in vitro antineoplastic properties; however, its effect on ovarian cancer cells is unknown. We evaluated the in vitro effect of gedunin on SKOV3, OVCAR4, and OVCAR8 ovarian cancer cell lines proliferation, alone and in the presence of cisplatin. Furthermore, we analyzed in vitro gedunin sensitivity data, integrated with genome-wide expression data from 54 cancer cell lines in an effort to identify genes and molecular pathways that underlie the mechanism of gedunin action. In vitro treatment of ovarian cancer cell lines with gedunin alone produced up to an 80% decrease in cell proliferation (P < 0.01) and, combining gedunin with cisplatin, demonstrated up to a 47% (P < 0.01) decrease in cell proliferation compared with cisplatin treatment alone. Bioinformatic analysis of integrated gedunin sensitivity and gene expression data identified 52 genes to be associated with gedunin sensitivity. These genes are involved in molecular functions related to cell cycle control, carcinogenesis, lipid metabolism, and molecular transportation. We conclude that gedunin has in vitro activity against ovarian cancer cells and, further, may enhance the antiproliferative effect of cisplatin. The molecular determinants of in vitro gedunin response are complex and may include modulation of cell survival and apoptosis pathways. ER -