Defense Date

2011

Document Type

Thesis

Degree Name

Master of Science

Department

Pharmacology & Toxicology

First Advisor

David Gewirtz

Abstract

The weak selectivity of chemotherapeutic drugs against tumors has sustained efforts to develop better chemotherapeutic agents that are more potent and selective at destroying tumor cell populations versus normal tissues. This project focuses on evaluating the cell killing effects of the microtubule inhibitor, stilbene 5c, against melanoma cancer. We utilized an in vitro murine melanoma model to study the effects of stilbene 5c on tumor proliferation and survival, as well as growth arrest and cell death. Our findings indicate that stilbene 5c promotes dose dependent cell death in melanomas with the induction of apoptosis and autophagy. The role of autophagy was further assessed using the pharmacological autophagy inhibitor, Bafilomycin A1. It was concluded that autophagy was partially cytoprotective as inhibition of autophagy was shown to induce extensive cell death through an increase in apoptosis. Residual surviving cells were shown to be in a state of growth arrest characterized to be senescence. These findings indicate that stilbene 5c could potentially be developed for the treatment of melanoma.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2011

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