A new plant-derived compound, Hu-17, induces apoptosis and chemosensitization of ovarian cancer cells to platinum through activation of ROS-mediated JNK signaling

Platinum-based compounds exert their anti-neoplastic effect through direct binding to DNA, which blocks fundamental cellular process ultimately resulting in apoptotic cell death. However, many ovarian cancers become refractory to treatment with platinum-based compounds. To improve the existing therapies for ovarian cancer, we sought to identify potent, nontoxic and specific drug candidates that have anti-neoplastic effects towards cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Using a cell-based screening assay, we evaluated 56 compounds-derived from the Chinese medicinal plant, Phytolaccae, and one phytoaccagenin compound (Hu-17) was selected on the basis of its ability to dramatically decrease the viability of cisplatin-resistant SK-OV-3 cells.Using high-throughtput microarray system, we identified GO terms and pathway signatures enriched in Hu-17 and/or cisplatin treated SK-OV-3 cells. Ovarian cancer cells SK-OV-3 were cultured in McCoy's 5A medium supplemented with 10% fetal bovine serum, the cell were treated with Hu-17 and/or cisplatin for different time, and total RNA from SK-OV-3 cells was hybridized on Affymetrix U133 plus 2.0 genechip.