Off-campus University of Richmond users: To download campus access theses, please use the following link to log in to our proxy server with your university username and password.

Date of Award

2014

Document Type

Restricted Thesis: Campus only access

First Advisor

Dr. Krista Stenger

Abstract

JG-03-14, a novel chemotherapeutic and polysubstituted pyrrole has shown to be a potent antiproliferative and proapoptotic agent in multiple cancer cell lines. Furthermore, while this compound has been shown to not promote peripheral neuropathy, its’ effects on the immune system have yet to be determined. This study aimed to further understand how JG-03-14 alters macrophage function by studying the effects of the compound on the production of the pro-inflammatory cytokine, TNF-α, and the reactive nitrogen species, nitric oxide. Exposure to JG-03-14 resulted in the attenuation of TNF-α secretion, as well as a decrease in inducible nitric oxide synthase (iNOS) leading to a reduction in the amount of nitric oxide (NO) produced by activated macrophages. Thus, the drug appears to possess some anti-inflammatory properties mediated partially by the destabilization of microtubules, leading to an alteration in vesicular transport, as well as through inhibition of NF-κB activation. Activation of the NF-κB transcription factor is required for the synthesis of pro-inflammatory proteins. The concentrations of JG-03-14 required to induce these effects were higher than what have been shown to be effective in cancer cell lines. These observations further strengthen JG-03-14’s potential utility as a novel anticancer agent.

Available for download on Saturday, May 18, 2019

Share

COinS