Date of Award

January 2016

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Nutrition Science

First Advisor

Silvia Stan

Committee Member 1

Jay Burgess

Committee Member 2

Nana Gletsu-Miller

Committee Member 3

Steven Konieczny

Abstract

With an increasing global cancer burden, new methods of cancer prevention are desired to improve overall survival. In particular, pancreatic cancer (PC) is in desperate need of new strategies to improve the dismal 8% overall 5-year survival rate. Studies have shown aberrant activation of the Hedgehog pathway to be associated with very poor prognosis in multiple cancer types, including pancreatic. Prevention strategies utilizing dietary agents have been shown to regulate multiple cancer hallmark pathways, but little is known regarding their effect on Hedgehog. Here we observed diallyl trisulfide (DATS), an anti-cancer agent found in garlic, reduced colony formation and inhibited Hedgehog signaling in PC cells. Treatment of AsPC-1 PC cells with DATS resulted in inhibition of mRNA and protein expression of the transcription factor Gli1. Protein levels of the Sonic Hedgehog pathway initiating ligand as well as the Patched receptor were increased following DATS treatment. Additionally, DATS reduced ectopic expression of Gli1. These results give further support for the anti-cancer role of DATS and provide rationale for future investigation into its use as a chemopreventive agent in PC.

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