Effects of Green Tea Catechins on Prostate Cancer Chemoprevention: The Role of the Gut Microbiome

Abstract

Accumulating evidence supports green tea catechins (GTCs) in chemoprevention for prostate cancer (PCa), a leading cause of cancer morbidity and mortality among men. GTCs include (-)-epigallocatechin-3-gallate, which may modulate the molecular pathways implicated in prostate carcinogenesis. Prior studies of GTCs suggested that they are bioavailable, safe, and effective for modulating clinical and biological markers implicated in prostate carcinogenesis. GTCs may be of particular benefit to those with low-grade PCas typically managed with careful monitoring via active surveillance (AS). Though AS is recommended, it has limitations including potential under-grading, variations in eligibility, and anxiety reported by men while on AS. Secondary chemoprevention of low-grade PCas using GTCs may help address these limitations. When administrated orally, the gut microbiome enzymatically transforms GTC structure, altering its bioavailability, bioactivity, and toxicity. In addition to xenobiotic metabolism, the gut microbiome has multiple other physiological effects potentially involved in PCa progression, including regulating inflammation, hormones, and other known/unknown pathways. Therefore, it is important to consider not only the independent roles of GTCs and the gut microbiome in the context of PCa chemoprevention, but how gut microbes may relate to individual responses to GTCs, which, in turn, can enhance clinical decision-making.

Keywords: chemoprevention; green tea catechins; microbiome; prostate cancer.

Figure 1

Mechanistic pathway by which GTCs prevent PCa progression. In vitro studies [41,42,43,44] demonstrate that GTCs block proteasomal activity in PCa cells, leading to build-up of proteasomal substrates Kip1 and Ik-b α that subsequently downregulate the activity of NF-κB. This inhibits the cell cycle and elicits apoptosis in these PCa cells. GTCs, green tea catechins; Ik-b α, NF-κB inhibitor alpha; NF-κB, nuclear factor kappa B; PCa, prostate cancer. Created with Biorender.com (accessed on 1 July 2022).

Figure 2

Examples of chemopreventive effects of GTCs in the context of PCa via gut microbiome modulation. (A) GTCs like EGCG have been evidenced to alter microbial composition, such as increasing abundance of Bifidobacterium [95]. This genus, for example, is known to increase production of SCFAs [95,96] which inhibit inflammatory pathways initiated by NF-κB that would otherwise propel carcinogenesis [97]. (B) The gut microbiome can enzymatically alter GTCs like EGCG to produce metabolites including gallic acid, EGC, valeric acid, and valerolactone, that subsequently travel to the bloodstream to exert potential chemopreventive benefits (e.g., regulating HDAC 1 and 2 and suppressing cell-cycle-related genes) [95,98,99,100]. EGC, epigallocatechin; EGCG, epigallocatechin gallate; GTCs, green tea catechins; HDAC, histone deacetylase; IL-6, interleukin-6; NF-κB, nuclear factor kappa B; SCFA, short chain fatty acid; TNF-α, tumor necrosis factor alpha. Created with Biorender.com (accessed on 1 July 2022).