Saponins are a class of secondary metabolites found in many plants and are frequently used as herbal medicine. Recently, a novel triterpenoid saponin (Y3) isolated from the plant Xanthoceras sorbifolia Bunge (Sapindaceae) was found to have cytotoxicity toward various human cancer cell lines. Among 12 human cell lines of different tissues origin, an ovarian cancer cell line, OVCAR3, has the lowest IC50 of 2.2µM while other cell lines have an IC50 between 7 to 20 µM. To further investigate the cytotoxicity of the isolated Y3 on ovarian cancer cells, an additional 8 ovarian cancer cell lines were tested. As determined by MTT assay, the IC50 values of Y3 for these ovarian cell lines are: OVCAR3 (2.2 µM), TOV-G21 (2.2 µM), ES2 (4.4 µM), OVCA432 (4.4 µM), Caov3 (7 µM), OVCA 429 (7 µM), RMG2 (8.8 µM), OVCA433 (8.8 µM), and SKOV3 (10.5 µM). To understand the molecular mechanism of the cytotoxic effect of Y3 on ovarian cancer cell, gene expression profiles were generated from ES2 cells treated with Y3 in triplicate experiments. From the expression profiles, angiopoietin-2 (ANGPT2), a naturally occurring inhibitor of angiogenesis, was found to be up-regulated by Y3. Furthermore, several genes: DDIT3, LIF and NFKB1Z, involved in apoptosis were also up-regulated. The up-regulation of these genes was validated by semi-quantitative real-time PCR. The anti-tumor effect of Y3 on ES2 cells was further tested in an orthotopic model. Athymic (nu/nu) mice were inoculated peritoneally with 106 ES2 cells. After 1, 4 and 10 days of inoculation, tumor bearing mice were injected peritoneally at a dosage of 2.5 mg/kg/day of Y3 for 10 days. The survival data from triplicate experiments was shown in table 1. Histological analysis of tumors from both untreated and Y3 treated tumor bearing mice indicated that fewer blood vessels were present in the tumors from treated mice. These results indicate that Y3 has an anti-tumor effect on ovarian cancer cells. The anti-tumor effect may via the activation of apoptotic pathways and the anti-angiogenesis pathway.$$table_{C9A67964-6843-4CDB-B96D-722A73F684F9}$$

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 167.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO