New insights into the mechanisms of green tea catechins in the chemoprevention of prostate cancer

Abstract

Prostate cancer is the most commonly diagnosed cancer and second most common cause of cancer deaths in American men. Its long latency, slow progression, and high incidence rate make prostate cancer ideal for targeted chemopreventative therapies. Therefore, chemoprevention studies and clinical trials are essential for reducing the burden of prostate cancer on society. Epidemiological studies suggest that tea consumption has protective effects against a variety of human cancers, including that of the prostate. Laboratory and clinical studies have demonstrated that green tea components, specifically the green tea catechin (GTC) epigallocatechin gallate, can induce apoptosis, suppress progression, and inhibit invasion and metastasis of prostate cancer. Multiple mechanisms are involved in the chemoprevention of prostate cancer with GTCs; understanding and refining models of fundamental molecular pathways by which GTCs modulate prostate carcinogenesis is essential to apply the utilization of green tea for the chemoprevention of prostate cancer in clinical settings. The objective of this article is to review and summarize the most current literature focusing on the major mechanisms of GTC chemopreventative action on prostate cancer from laboratory, in vitro, and in vivo studies, and clinical chemoprevention trials.

FIG. 1

Cumulative molecular model for the mechanism of green tea catechins in the chemoprevention of prostate cancer. Epigallocatechin gallate (EGCG) is the most potent catechin present in green tea. Green tea catechins (GTCs), particularly EGCG, inhibit the chymotrypsin-like activity of the proteasome resulting in the accumulation proteasome targets p21, p27, Bax, and IκBα. The accumulation of cell cycle regulators, p21 and p27, cause cell cycle arrest; while the accumulation of the proapoptotic protein, Bax, contributes to cancer cell apoptosis. Additionally, the elevation of IκBα expression inhibits the translocation of the oncogenic protein, NFκB, to the nucleus, resulting in reduced expression of its target genes, Bcl-xL and Bcl-2, cyclin D and cyclin E, VEGF, and MMPs. Reductions in these proteins further drive the processes of cell cycle arrest, decreased cell proliferation, and apoptosis, as well as the inhibition of tumor cell invasion and metastasis, respectively. The cumulative effect of these mechanisms leads to the inhibition of prostate cancer progression and metastasis. All proteins shown are affected by GTC treatment of prostate cancer cells and tissues in laboratory and/or clinical studies. The up arrow indicates induction; while the down arrow indicates reduction in protein expression upon GTC treatment. FLIP indicates FLICE-inhibitory proteins; IκBα, inhibitor of IκBα; IAP, inhibitor of apoptosis; MMP, matrix metalloproteinase; NFκB, nuclear factor kappa B; uPA, urokinase-type plasminogen activator; VEGF, vascular endothelial growth factor; XIAP, x-linked inhibitor of apoptosis.