Chemoprevention of Human Prostate Cancer by Oral Administration of Green Tea Catechins in Volunteers with High-Grade Prostate Intraepithelial Neoplasia: A Preliminary Report from a One-Year Proof-of-Principle Study

Abstract

Green tea catechins (GTCs) proved to be effective in inhibiting cancer growth in several experimental models. Recent studies showed that 30% of men with high-grade prostate intraepithelial neoplasia (HG-PIN) would develop prostate cancer (CaP) within 1 year after repeated biopsy. This prompted us to do a proof-of-principle clinical trial to assess the safety and efficacy of GTCs for the chemoprevention of CaP in HG-PIN volunteers. The purity and content of GTCs preparations were assessed by high-performance liquid chromatography [(À)-epigallocathechin, 5.5%; (À)-epicatechin, 12.24%; (À)-epigallocatechin-3-gallate, 51.88%; (À)-epicatechin-3-gallate, 6.12%; total GTCs, 75.7%; caffeine, <1%]. Sixty volunteers with HG-PIN, who were made aware of the study details, agreed to sign an informed consent form and were enrolled in this double-blind, placebo-controlled study. Daily treatment consisted of three GTCs capsules, 200 mg each (total 600 mg/d). After 1 year, only one tumor was diagnosed among the 30 GTCs-treated men (incidence, f3%), whereas nine cancers were found among the 30 placebo-treated men (incidence, 30%). Total prostate-specific antigen did not change significantly between the two arms, but GTCs-treated men showed values constantly lower with respect to placebotreated ones. International Prostate Symptom Score and quality of life scores of GTCs-treated men with coexistent benign prostate hyperplasia improved, reaching statistical significance in the case of International Prostate Symptom Scores. No significant side effects or adverse effects were documented. To our knowledge, this is the first study showing that GTCs are safe and very effective for treating premalignant lesions before CaP develops. As a secondary observation, administration of GTCs also reduced lower urinary tract symptoms, suggesting that these compounds might also be of help for treating the symptoms of benign prostate hyperplasia.

Effect of Sulforaphane in Men with Biochemical Recurrence after Radical Prostatectomy

“…Nevertheless, clinical evidence is scarce and provides conflicting results for the effects of these compounds. In a double-blind placebo-controlled study, green tea catechins (GTC) significantly prevented prostate cancer development in men with highgrade premalignant prostate intraepithelial neoplasia (42). Two randomized, double-blind, placebo-controlled short-term isoflavone intervention trials before radical prostatectomy have shown that genistein failed to change the PSA levels significantly, even though it modulated the expression of several genes involved in prostate cancer (43,44).…”

Ornithine Decarboxylase Is Sufficient for Prostate Tumorigenesis via Androgen Receptor Signaling

“…Although a phase 2 clinical trial of DFMO with patients with a family history of prostate cancer but no previous personal history of prostate cancer has been reported, 55 no trials have included patients with a diagnosis of HGPIN and no evidence of prostate cancer. Different chemopreventive clinical trials have been developed to control progression of HGPIN to prostate cancer using selenium, soy, vitamin E, 56,57 toremifene, 58 or green tea extract, 59,60 with different success rates. Our findings suggest that DFMO treatment, which is usually associated with minimal toxicity, 61 may prove valuable for reducing the development of prostate cancer in patients with a diagnosis of HGPIN and may play a crucial role in future chemopreventive clinical trials.…”

Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis

“…The use of phytonutrient as anticancer agents has gained considerable importance in recent years. Several studies from our laboratory and by others have suggested that green tea, especially its constituent polyphenols possess chemopreventive and therapeutic potential against CaP (Jian et al, 2004;Bettuzzi et al, 2006;Siddiqui et al, 2006Siddiqui et al, , 2007. Much of the anticancer and/or cancer chemopreventive effects of green tea are attributed to be mediated by its major polyphenol(À)epigallocatechin-3-gallate (EGCG) ; and the references therein).…”