Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion

Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has been demonstrated to possess anti-inflammatory, antioxidant, anti-mutagenic and anti-carcinogenic properties. The anti-melanoma effect of EGCG has been previously suggested, but no clear mechanism of action has been established. In this study, we demonstrated that EGCG inhibits melanoma cell growth at physiological doses (0.1-1 mu M). In the search for mechanisms of EGCG-mediated melanoma cell suppression, we found that NF-kappa B was inhibited, and that reduced NF-kappa B activity was associated with decreased IL-1 beta secretion from melanoma cells. Since inflammasomes are involved in IL-1 beta secretion, we investigated whether IL-1 beta suppression was mediated by inflammasomes, and found that EGCG treatment led to downregulation of the inflammasome component, NLRP1, and reduced caspase-1 activation. Furthermore, silencing the expression of NLRP1 abolished EGCG-induced inhibition of tumor cell proliferation both in vitro and in vivo, suggesting a key role of inflammasomes in EGCG efficacy. This paper provides a novel mechanism for EGCG-induced melanoma inhibition: inflammasome downregulation -> decreased IL-1 beta secretion -> decreased NF-kappa B activities -> decreased cell growth. In addition, it suggests inflammasomes and IL-1 beta could be potential targets for future melanoma therapeutics. Published by Elsevier Inc.