Epigallocatechin-3-Gallate suppresses early stage, but not late stage prostate cancer in TRAMP mice: Mechanisms of action

• Published in: The Prostate Vol. 67; no. 14; pp. 1576 - 1589
• Main Authors: Harper, Curt E., Patel, Brijesh B., Wang, Jun, Eltoum, Isam A., Lamartiniere, Coral A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2007
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Animals; Anticarcinogenic Agents - blood; Anticarcinogenic Agents - pharmacology; Apoptosis - drug effects; Catechin - analogs & derivatives; Catechin - blood; Catechin - pharmacology; Cell Proliferation - drug effects; chemoprevention; Drug Screening Assays, Antitumor; EGCG; IGF-1; Insulin-Like Growth Factor I - metabolism; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Mice, Transgenic; Prostate - drug effects; Prostate - pathology; prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Receptor, IGF Type 1 - drug effects; Receptor, IGF Type 1 - metabolism; Receptors, Androgen - drug effects; Receptors, Androgen - metabolism; TRAMP
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20643

BACKGROUND Prostate cancer (PCa) is the second leading cause of cancer‐related death in men in the United States. Many men have implemented purported chemopreventive agents into their daily diet in an attempt to delay the early onset of a PCa. Green tea polyphenols, one such agent, has been shown to be chemopreventive in skin, breast, and prostate cancers. We hypothesized that Epigallocatechin‐3‐Gallate (EGCG), the major polyphenol found in green tea, will exert its chemopreventive effect in the prostate via regulation of sex steroid receptor, growth factor‐signaling, and inflammatory pathways. METHODS Five‐week‐old male TRAMP (Transgenic Adenocarcinoma Mouse Prostate) offspring were fed AIN‐76A diet and 0.06% EGCG in tap water. Animals were sacrificed at 28 weeks of age and the entire prostates were scored histopathologically. In addition, animals were sacrificed at 12 weeks of age and ventral (VP) and dorsolateral (DLP) prostates were removed for histopathological evaluation and immunoblot analyses or ELISA. RESULTS EGCG, inhibited early but not late stage PCa in the current study. In the VP, EGCG significantly reduced cell proliferation, induced apoptosis, and decreased androgen receptor (AR), insulin‐like growth factor‐1 (IGF‐1), IGF‐1 receptor (IGF‐1R), phospho‐extracellular signal‐regulated kinases 1 and 2 (phospho‐ERKs 1 and 2), cyclooxygenase‐2 (COX‐2), and inducible nitric oxide synthase (iNOS). CONCLUSIONS The attenuation of the AR, the down‐regulation of potent growth factor IGF‐1, modulation of inflammation biomarkers, and decrease in the MAPK signaling may contribute to the reduction in cell proliferation and induction of apoptosis and hence provide a biochemical basis for EGCG suppressing PCa without toxicity. Prostate 67: 1576–1589, 2007. © 2007 Wiley‐Liss, Inc.