Journal
PHARMACEUTICAL RESEARCH
Volume 25, Issue 9, Pages 2135-2142Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-008-9553-z
Keywords
green tea; NF kappa B; osteopontin; RANK; TRAMP
Funding
- US PHS [R01 CA 78809, R01 CA 101039, R01 CA 120451]
- O'Brian center [P50 DK065303-01]
- NATIONAL CANCER INSTITUTE [R01CA101039, R01CA120451, R01CA078809] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P50DK065303] Funding Source: NIH RePORTER
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Purpose. This study examines the role of cell survival/apoptosis related proteins involved in NF kappa B signaling pathways and its associated events in GTP-induced chemoprevention of prostate cancer in TRAMP mice. Methods. Mice were given 0.1% GTP as drinking fluid. Western blot and immunohistochemical analysis performed to examine NF kappa B and its regulated pathway in response to GTP. Results. Our data demonstrated increased expression of NF kappa B, IKK alpha, IKK beta, RANK, NIK and STAT-3 in dorso-lateral prostate of TRAMP mice as a function of age and tumor growth and continuous GTP infusion for 32 weeks resulted in substantial reduction in these proteins. The levels of transcription factor osteopontin, a non-collagenous extracellular matrix protein, were also downregulated. Inhibition of NF kappa B signaling is known to activate apoptotic and inhibit anti-apoptotic proteins. Therefore, we analyzed Bax and Bcl(2) levels in the dorsolateral prostate of TRAMP mice fed GTP and observed a shift in balance between Bax and Bcl(2) favoring apoptosis. Conclusions. Based on the data we suggest that oral consumption of GTP might inhibit osteopontin and NF kappa B signaling that may contribute to induction of apoptosis observed in GTP fed TRAMP mice.
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