Purpose: This study examines the role of cell survival/apoptosis related proteins involved in NFkappaB 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 NFkappaB and its regulated pathway in response to GTP.
Results: Our data demonstrated increased expression of NFkappaB, IKKalpha, IKKbeta, 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 NFkappaB signaling is known to activate apoptotic and inhibit anti-apoptotic proteins. Therefore, we analyzed Bax and Bcl2 levels in the dorsolateral prostate of TRAMP mice fed GTP and observed a shift in balance between Bax and Bcl2 favoring apoptosis.
Conclusions: Based on the data we suggest that oral consumption of GTP might inhibit osteopontin and NFkappaB signaling that may contribute to induction of apoptosis observed in GTP fed TRAMP mice.