Abstract 1251: Repurposing antipsychotic drug Penfluridol for cancer treatment

Abstract

Abstract Repurposing of old drugs as new anti-cancer drugs is important as it can save time and cost of drug development. Penfluridol is a first generation, highly potent antipsychotic drug. In this study, we determined the anticancer effects of Penfluridol in pancreatic cancer cells. Penfluridol treatment inhibited the growth of Panc-1, BxPC-3 and AsPC-1 pancreatic cancer cells in a concentration-dependent manner. Panc-1 , BxPC-3 and AsPC-1 cells treated with Penfluridol exhibited apoptosis as evaluated by Annexin/FITC assay and cleavage of caspase-3 and PARP. Our results showed that Penfluridol treatment induced ER stress in pancreatic cancer cells through the up regulation of ER stress markers like Bip/Grp78, CHOP and IRE. Penfluridol treatment also induced autophagy in pancreatic cancer cells as observed by acridine orange assay. Western blot analysis of Panc-1, BxPC-3 and AsPC-1 cells treated with Penfluridol exhibited up regulation of autophagy markers like LC3B, and p62. Microscopic analysis revealed punctate LC3B after Penfluridol treatment in pancreatic cancer cells confirming autophagy. Further mechanistic studies are in progress to establish the role of ER stress and autophagy in pancreatic cancer cells and correlate it with cell growth suppression. [Supported in part by R01 grant CA129038 awarded by NIH.] Citation Format: Alok Ranjan, Sanjay K. Srivastava. Repurposing antipsychotic drug Penfluridol for cancer treatment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1251. doi:10.1158/1538-7445.AM2014-1251