Abstract
Abstract Pancreatic cancer is the fourth leading cause of cancer death and without effective medical therapy. New agents acting on novel targets need to be developed. Natural products provide a promising source for developing effective anticancer agents. Oleanolic acid (OA) and ursolic acid (UA) are two natural triterpenoids with reported antitumor activities in several types of cancer. The antitumor effects of OA, oleanolic acid methyl ester (OAME) and UA were determined in pancreatic cancer Aspc-1 cells. Cell growth inhibition of the three compounds was determined using the MTT assay. The IG50s of OA, OAME and UA after treatment with UA for 4 days are >30, 8.9, 12.5 μM, respectively. OA is a weak cell growth inhibitor and methyl esterification improves its antitumor activity. UA is more effective than OA to inhibit cell growth in Aspc-1 cells and was used to study the mechanism of action. Aspc-1 cells treated with UA at a concentration higher than 25 uM induced apoptosis as determined by PARP cleavage detection. Western blot analysis revealed that the levels of procaspase-3, -9 and Bcl-XL were markedly decreased while the levels of Mcl-1, XIAP and survivin were weakly or not decreased. Correlated with the decrease in the level of Bcl-XL, the level of phosphorylated STAT3 was significantly inhibited. STAT3 is activated in pancreatic cancer cells and contributes to pancreatic tumorigenesis. Activated STAT3 increases the levels of antiapoptotic protein such as Bcl-XL, Mcl-1 and survivin, are being considered as a target for developing agents for pancreatic cancer treatment. Our data suggest that UA is a lead candidate for targeting STAT3 and structural modification of UA may result in a new group of compounds with improved antitumor activity in pancreatic cancer cells. 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 4234. doi:10.1158/1538-7445.AM2011-4234
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