Advisory Committee Chair
Coral Lamartiniere
Advisory Committee Members
Stephen Barnes
Ada Elgavish
Isam Eltoum
Clinton Grubbs
Document Type
Dissertation
Date of Award
2007
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Prostate cancer is the second leading cause of cancer-related death among men in the United States. The goal of this research was to investigate the potential of three nutriceutical polyphenols, genistein, resveratrol, and epigallocatechin-3-gallate (EGCG), to suppress prostate cancer. Cancer chemoprevention and mechanism of action studies were carried out in transgenic models of prostate cancer. In TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, resveratrol suppressed poorly differentiated tumors by 86%, whereas EGCG suppressed precancerous lesions, but failed to prevent late-stage prostate cancer. Agents that were chemopreventive in the TRAMP model were subsequently evaluated alone, and in combination, in the newly developed SV-40 Tag transgenic rat model. Genistein and resveratrol, alone and in combination, suppressed prostate cancer in SV-40 Tag transgenic rats, but not in an additive or synergistic manner when compared to the single agent treatments. Using immunoassay techniques, we demonstrated a reduction in cell proliferation and an induction of apoptosis in polyphenol-treated animals. We also found down-regulation of growth factor signaling and a modulation of sex steroid receptors. Specifically, all polyphenols reduced insulinlike growth factor-1 protein expression and its downstream effector, phosphoextracellular signal regulated kinase in the prostate. Genistein and EGCG down-regulated androgen receptor, whereas genistein decreased epidermal growth factor receptor and ii resveratrol up-regulated proposed tumor suppressor, estrogen receptor-β protein expression. We determined genistein and resveratrol concentrations in blood serum via HPLC/MS to be 2160 nM and 212 nM in genistein- and resveratrol-treated rats, respectively. The regulation of biomarkers known to play a role in prostate carcinogenesis, alterations in cell turnover, and high, but biologically achievable concentrations of polyphenols in the blood most likely account for the chemoprevention observed. In summary, genistein and resveratrol are promising weapons in the fight against prostate cancer and the SV-40 Tag transgenic rat model is a useful tool in evaluating the chemopreventive properties of potential agents.
Recommended Citation
Harper, Curt E., "Prostate Cancer Chemoprevention With Genistein And Resveratrol In Models Of Spontaneously Developing Prostate Cancer" (2007). All ETDs from UAB. 3714.
https://digitalcommons.library.uab.edu/etd-collection/3714