Abstract 616: A cumulative molecular model for the mechanisms of green tea catechins in the chemoprevention of prostate cancer

Abstract

Abstract Background: Prostate cancer (CaP) is the most commonly diagnosed cancer in men. It's long latency, slow progression, and high incidence rates make it ideal for targeting chemoprevention therapies. Studies suggest that green tea may be suitable candidate for CaP chemoprevention. The green tea catechin (GTC) chemopreventive mechanisms against CaP cells, however, are not completely clear. Understanding and refining models of the fundamental molecular pathways by which GTCs modulate prostate carcinogenesis is essential to most appropriately utilize green tea for CaP prevention in clinical settings. Objective: The objective of the study was to review the current literature and develop a model that attempts to recreate the molecular mechanisms and pathways by which GTCs modulate prostate carcinogenesis. Methods: Laboratory studies, clinical studies, and clinical trials focused on GTC chemoprevention of CaP were critically analyzed and reviewed for mechanisms of GTC chemoprevention. The most prevalent mechanisms were combined into a multi-mechanistic model that attempts to recreate the cumulative events that occur as GTCs exert anti-cancer activity on prostate cancer cells and tissues. Results: GTCs exert anti-cancer actions on CaP cells and tissue through six major mechanisms: proteasome inhibition, cell cycle arrest, inhibition of cell proliferation, induction of apoptosis, suppression of carcinogenesis/progression, and inhibition of metastasis. We have proposed a novel model in which GTCs exert chemopreventive effects on CaP though these six major mechanisms that work simultaneously and dependently, largely driven by proteasome inhibition-induced regulation of the NFκB pathway. The cumulative effect of these mechanisms ultimately leads to the inhibition of CaP cell growth, progression, and metastasis. Conclusions: Several mechanisms of GTC chemopreventive activity on CaP cells and tissues have been identified in laboratory and clinical studies. Although GTCs act through distinct cell cycle regulative pathways, the cumulative chemopreventative effect appears to be attributed to their well-coordinated ensemble, rather than a single pathway. Additionally, transitioning to the use of standardized GTC preparations may more accurately reflect human tea consumption, deliver the maximum amount of GTCs, and allow for more generalizable results in epidemiological, laboratory, and clinical studies. We are currently testing and refining our novel cumulative model to fully elucidate the complex mechanism of GTC chemoprevention of prostate cancer in its entirety. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 616. doi:1538-7445.AM2012-616