title: BITC Sensitizes Pancreatic Adenocarcinomas to TRAIL-induced Apoptosis.
abstract: 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 often associated with mutations in 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 vegetables 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 dual activation of both the extrinsic and intrinsic apoptotic pathways.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Wicker
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Sahu
authors.forename: Kashmira
authors.initials: K
authors.lastname: Kulkarni-Datar
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Srivastava
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Brown