Date of Award

Fall 11-16-2017

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Nutrition

First Advisor

Dr. Huanbiao Mo

Second Advisor

Dr. Desiree Wanders

Third Advisor

Dr. Weiming Xia

Abstract

Background: Approximately one in seven American men will be diagnosed with prostate cancer during their lifetime. The mevalonate pathway produces essential intermediates for the post-translational prenylation and dolichylation of growth-associated proteins including Ras, nuclear lamins and growth factor receptors. Dysregulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme of the mevalonate pathway, in prostate cancer cells supports tumor growth and therefore can be targeted for prostate cancer prevention and therapy. Previous studies have shown that isoprenoids including tocotrienols and xanthorrhizol suppress the growth of prostate cancer cells with concomitant downregulation of HMG CoA reductase.

Objective: To determine the synergistic effects of d-δ-tocotrienol and xanthorrhizol on growth of human DU-145 prostate carcinoma cells.

Methods: DU-145 cells were incubated with d-δ-tocotrienol and xanthorrhizol, individually and in blends, for 72 hours before viable cells were quantified by CellTiter 96® Aqueous One Solution. The impacts of these compounds, individually and in combination, on cell cycle distribution and the

expression of cell cycle related proteins in DU-145 cells were evaluated by flow cytometry and Western-blot in follow-up studies.

Statistical analysis: All experiments were repeated 3 times. One-way analysis of variance (ANOVA) was performed to assess the differences between groups using PrismⓇ 4.0 software (GraphPad Software Inc., San Diego, CA). Differences in means was assessed using Tukey’s test. Levels of significance are indicated as P < 0.05.

Results: Blends of d-δ-tocotrienol and xanthorrhizol showed greater inhibition of cell growth than those of individual compounds. Current results did not show a significant change in cell cycle distribution or down regulation of Cdk4 and cyclin D1 with the combination of compounds. The level of procaspase-3 for apoptosis initiation was also not altered.

Conclusion: Further studies are warranted to confirm these initial findings and understand the mechanisms underlying the combined effect of d-δ-tocotrienol and xanthorrhizol on cell proliferation.

DOI

https://doi.org/10.57709/11093046

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