SENSITIZATION TO TRAIL-INDUCED APOPTOSIS IN K-RAS 12 MUTANT PANCREATIC CANCER CELLS BY BITC

by Wicker, Christina Ann

Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95% mortality rate and short survival after diagnosis. Chemotherapeutic resistance hinders successful treatment. This resistance is associated with mutations within codon 12 of the K-Ras gene (K-Ras 12), which is present in over 90% of all pancreatic adenocarcinomas. Codon 12 mutations maintain Ras in a constitutively active state leading to continuous cellular proliferation. Our study determined if TRAIL resistance in pancreatic adenocarcinomas with K-Ras 12 mutations could be overcome by first sensitizing the cells with Benzyl isothiocyanate (BITC). BITC is a component of cruciferous vegetable extracts and a cell cycle inhibitor. BxPC3, MiaPaCa2, and Panc-1 human pancreatic adenocarcinoma cell lines were examined for TRAIL resistance. Our studies show BITC-induced TRAIL sensitization by the activation of caspases 8, 9 and 3 as well as their respective substrates Bid, XIAP, and PARP. Cell Death ELISA confirmed TRAIL sensitization by BITC.