Date of Award

Fall 2000

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry & Biochemistry

Program/Concentration

Chemistry

Committee Director

Roy L. Williams

Committee Member

Steven J. Beebe

Committee Member

Mark S. Elliott

Call Number for Print

Special Collections LD4331.C45 M67

Abstract

Recently attention has been brought to trans-resveratrol's {TR) anticancer activity, as determined through a number of cultured cancer cell models. This activity was attributed to TR behaving as an estrogen, and the orientation of TR' s hydroxyl groups. Based on this work it was of interest to determine whether TR would also be toxic in prostate cancer cells; if toxic, did TR induce necrosis or apoptosis in the cells; was it toxic through hormone mediated pathways; and were TR's hydroxyl groups responsible for its biological activity. To this end, cellular viability was assessed in two different prostate cancer cell lines, LNCaP and DU 145, in the presence of TR. The onset of apoptosis in LNCaP cells treated with TR was also measured through three distinct techniques, which measured apoptotic morphology, phosphatidylserine (PS) externalization and caspase activity, three events that occur in cells undergoing apoptosis. The measurement of apoptotic morphology and PS externalization, distinguished between apoptotic and necrotic cells. An immuno blot was also used to determine which of two possible caspases were being activated. Trimethoxy-TR (Tm TR), a methylated TR analogue, was synthesized to determine whether TR' s hydroxyl groups were important to its biological activity. It was found through the cell viability assays that, although TR was toxic to LNCaP cells, it was not toxic only through hormone mediated pathways. It was also found that TR induced apoptosis in LNCaP cells in all three assays used, and that apoptosis was taking place through caspase-3. Finally it was determined that TR's hydroxyl groups were important to its biological activity.

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DOI

10.25777/82z2-gx31

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