Abstract B68: Antioxidant activity of green tea: A phase II clinical trial in men with prostate cancer

Abstract

Background: Green tea (GT) contains green tea polyphenols (GTPs) which have been shown to play a role in the regulation of cell proliferation and apoptosis in prostate cancer cells in vitro and in animal models using human prostate cancer cell xenografts. GTPs are also potent scavengers of reactive oxygen species (ROS) which play a role in tumorigenesis. While there is extensive epidemiological and basic science evidence for these effects of GTPs, data from human intervention studies is much more limited. Objective: We conducted a phase II intervention study to evaluate the anticarcinogenic and antioxidant effects of green tea in prostate cancer by administering green tea in men prior to prostatectomy. Design: 79 men, diagnosed with prostate cancer and scheduled for prostatectomy, were randomized to either 6 cups of brewed green tea (GT group, N=34) or water (control group, N=33) daily for 3-8 weeks prior to surgery. 67 men completed the intervention. Blood and urine samples were collected before and after the intervention, and a section of prostate tissue was obtained following the pathology evaluation. Serum prostate specific antigen (PSA) concentration was determined by ELISA assay and prostate tissue PSA protein concentration was measured by Western blot. The prostate concentration of GTPs and their metabolites was measured using high-performance liquid chromatography (HPLC) with CoulArray electrochemical detection. The concentration of 8-hydroxydeoxyguanosine (8-OHdG), a biomarker for oxidative DNA damage, was measured in urine by HPLC. In addition, gene expression of the antioxidant enzymes superoxide dismutase (SOD) and catalase were determined in normal and tumor prostate tissue using real-time quantitative PCR. Results: Statistical analysis within each treatment arm showed that the serum PSA concentration significantly decreased in the GT group (final vs. baseline blood) (P<0.01), while no change was observed in the control group. The comparison of percent change in serum PSA between GT and control group showed a decreasing trend (p=0.085). Prostate tissue PSA protein expression was lower in men consuming GT compared to water control (p=0.06). The major bioactive component of GTPs, epigallocatechin gallate (EGCG) and its methyl metabolite 4″-O-methyl EGCG were found in prostate tissue in similar amounts, along with a small amount of epicatechin gallate. As compared to the pre-intervention level there was a significant decrease in urinary 8-OHdG concentration after GT intervention (83 vs. 50 nmol/g creatinine), while there was no change in the control group (54 vs. 55 nmol/g creatinine). Gene expression of SOD (p=0.087) and catalase (p=0.15) in the prostate tumor tissue normalized to normal prostate tissue in each individual showed a decreasing trend in men consuming GT as compared to the water control. Conclusion: The consumption of 6 cups of GT provided antioxidant protection, which may contribute to an inhibitory effect on prostate tumor growth in humans. Large-scale human intervention studies are needed to confirm these findings. Citation Format: Piwen Wang, William Aronson, Narine Abgaryan, Catherine L. Carpenter, Jaydutt V. Vadgama, David Heber, Susanne M. Henning. Antioxidant activity of green tea: A phase II clinical trial in men with prostate cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B68.