Effective Prostate Cancer Chemopreventive Intervention with Green Tea Polyphenols in the TRAMP Model Depends on the Stage of the Disease

• Published in: Clinical cancer research 2009-03, Vol.15 (6), p.1947-1953
• Main Authors: VAQAR MUSTAFA ADHAMI, LMTIAZ AHMAD SIDDIQUI, SARFARAZ, Sami, SABIH ISLAM KHWAJA, BILAL BIN HAFEEZ, AHMAD, Nihal, MUKHTAR, Hasan
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - chemistry; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - prevention & control; Animals; Anticarcinogenic Agents - therapeutic use; Antineoplastic agents; Biological and medical sciences; chemoprevention; Disease Models, Animal; Female; Flavonoids - therapeutic use; green tea; Gynecology. Andrology. Obstetrics; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor I - analysis; Insulin-Like Growth Factor I - physiology; Magnetic Resonance Imaging; Male; Male genital diseases; Medical sciences; Mice; Mice, Inbred C57BL; Neoplasm Staging; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Phenols - therapeutic use; Polyphenols; prostate cancer; Prostatic Intraepithelial Neoplasia - prevention & control; Prostatic Neoplasms - chemistry; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Prostatic Neoplasms - prevention & control; stage; Tea; TRAMP; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-2332

Purpose: We have shown previously that oral feeding of green tea polyphenols (GTP) to transgenic adenocarcinoma of the mouse prostate mice in a purely chemopreventive setting significantly inhibits prostate cancer development. To translate this to a human situation, the present study was designed to identify the stage of prostate cancer that is most vulnerable to chemopreventive intervention by GTP. Experimental Design: GTP infusion (0.1% in drinking water) to transgenic adenocarcinoma of the mouse prostate was initiated at ages representing different stage of the disease: ( a ) 6 weeks (group 1, normal prostate), ( b ) 12 weeks (group 2, prostatic intraepithelial neoplasia), ( c ) 18 weeks (group 3, well-differentiated adenocarcinoma), and ( b ) 28 weeks (group 4, moderately differentiated adenocarcinoma). At age 32 weeks, subsets of animals were evaluated by magnetic resonance imaging, ultrasound, and prostate weight and for serum insulin-like growth factor (IGF)-I/IGF binding protein-3 and IGF signaling. Results: Tumor-free survival was extended to 38 weeks ( P < 0.001) in group 1, 31 weeks ( P < 0.01) in group 2, and 24 weeks ( P < 0.05) in group 3 compared with 19 weeks in water-fed controls. Median life expectancy was 68 weeks in group 1, 63 weeks in group 2, 56 weeks in group 3, and 51 weeks in group 4 compared with 42 weeks in the control mice. IGF-I and its downstream targets including phosphatidylinositol 3-kinase, pAkt, and phosphorylated extracellular signal-regulated kinase were significantly inhibited only when intervention was initiated early when prostatic intraepithelial neoplasia lesions were common. Conclusions: Our studies indicate that chemopreventive potential of GTP decreases with advancing stage of the disease and underscore the need to design appropriate chemoprevention clinical trails.