Publication Date
2008
Document Type
Thesis
Committee Members
Nancy Bigley (Committee Member), Thomas Brown (Advisor), Courtney Sulentic (Committee Member)
Degree Name
Master of Science (MS)
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 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.
Page Count
92
Department or Program
Department of Neuroscience, Cell Biology & Physiology
Year Degree Awarded
2008
Copyright
Copyright 2008, all rights reserved. This open access ETD is published by Wright State University and OhioLINK.
