Date of Award

Spring 5-21-2018

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Joann Powell, Ph.D.

Second Advisor

Nathan Bowen, Ph.D.

Third Advisor

Valerie Odero-Marah, Ph.D.

Abstract

The androgen receptor’s (AR) resurgence following treatment leads to castration resistant prostate cancer (CRPC). Studies show that the aryl hydrocarbon receptor (AhR) regulates AR signaling, is constitutively active, and enhances AR signaling in CRPC. AhR has ligands with carcinogenic properties and interacts with phytochemicals with anti-tumorigenic properties. Curcumin inhibits AhR activity and multidrug transporter ABCG2 activity, which mediates substrates out of the cell. Elevated ABCG2 expression causes resistance to anticancer drugs. AhR transcriptionally activates ABCG2 and our hypothesis is that inhibition of AhR activity by curcumin will decrease ABCG2 expression and activity in CRPC cells. C4-2 cells were treated with increasing concentrations of curcumin (0, 10, 25, 50µM) and CH223191 (50µM). Results show that curcumin decreases AhR, CYP1B1 and ABCG2 gene expression. Higher concentrations of curcumin diminish AhR and ABCG2 protein expression, ABCG2 activity, and cell proliferation. These results will help reveal a role for AhR in drug resistance.

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