Pancreatic ductal adenocarcinoma (PDA) is a highly lethal human malignancy with dismal prognosis and few effective therapeutic options. Novel agents that are safe and effective are urgently needed. Oleanolic acid-derived synthetic triterpenoids are potent antitumorigenic agents, but their efficacy for pancreatic cancer has not been investigated. We have found that methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me), a oleanane-derived synthetic triterpenoid exhibits potent anticancer activity against human pancreatic cancer cell lines. CDDO-Me inhibited the growth of both K-ras mutated (MiaPaca2, Panc1 and Capan2) and wild-type K-ras (BxPC3) pancreatic cancer cells at very low concentrations. The growth inhibitory activity of CDDO-Me was due to the induction of apoptosis characterized by increased annexin-V-FITC and cleavage of PARP-1 and procaspases-3, -8 and-9. Killing of PDA cells by CCDO-Me involved the generation of reactive oxygen species (ROS) as determined from the oxidation of H2DCFD by flow cytometry and its inhibition by general purpose antioxidant NAC. CDDO-Me was also highly active against gemcitabine resistant MiaPaCa2 cells expressing markers of tumor-initiating cells (cancer stem-like cells?). An ongoing pilot experiment has shown the antitumor activity of CDDO-Me against BxPC3 xenograft in vivo. Together, these data demonstrated potential of CDDO-Me for treating pancreatic cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3549. doi:10.1158/1538-7445.AM2011-3549