Suppression of NFκB and its Regulated Gene Products by Oral Administration of Green Tea Polyphenols in an Autochthonous Mouse Prostate Cancer Model

Abstract

Purpose-This study examines the role of cell survival/apoptosis related proteins involved in NFκB 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 NFκB and its regulated pathway in response to GTP.Results-Our data demonstrated increased expression of NFκB, IKKα, IKKβ, 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 NFκB signaling is known to activate apoptotic and inhibit antiapoptotic 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 NFκB signaling that may contribute to induction of apoptosis observed in GTP fed TRAMP mice.

Osteopontin: An Effector and an Effect of Tumor Metastasis

“…The administration of green tea polyphenols caused a decrease in the levels of OPN in TRAMP mice [180]. This was attributed to reduce levels and activity of NF-B, a transcription factor that upregulates OPN expression [92].…”

Tea polyphenols inhibit cyclooxygenase-2 expression and block activation of nuclear factor-kappa B and Akt in diethylnitrosoamine induced lung tumors in Swiss mice

“…In view of these reports, down-regulation of NF-κB by tea polyphenols might be correlated with induction of apoptosis and thus contributes to its anti-cancer effects in DEN-induced lung tumors. Inhibition of NF-κB by tea polyphenols has been reported in vitro and in vivo conditions [43][44][45]. Nam et al [46] reported that Epigallocatechin-3-gallate (EGCG) the major constituent of GTPs, inhibits proteasome function, a mechanism known to inhibit NF-κB activity, at concentrations of EGCG that are seen in the serum of green tea drinkers, suggesting its role in treatment also.…”

Modulation of signaling pathways in prostate cancer by green tea polyphenols

“…There was increased expression of NF-κB, IKKα, IKKβ, RANK, NIK and STAT-3 in dorsolateral prostate of TRAMP mice as a function of age and tumor growth and continuous GTP treatment caused significant decrease in the levels of these proteins. There was also a shift in the balance between Bax and Bcl2 proteins favoring apoptosis by GTP treatment via inhibition of NF-κB signaling [15]. Hsu et al, [16] have recently examined the effects of dietary soy and tea on NF-κB activation and inflammation in-vivo using male Noble rats implanted with estradiol and testosterone, which is a hormone-induced rat model for PCa.…”