title: Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion.
abstract: 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 μM). In the search for mechanisms of EGCG-mediated melanoma cell suppression, we found that NF-κB was inhibited, and that reduced NF-κB activity was associated with decreased IL-1β secretion from melanoma cells. Since inflammasomes are involved in IL-1β secretion, we investigated whether IL-1β 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-1β secretion→decreased NF-κB activities→decreased cell growth. In addition, it suggests inflammasomes and IL-1β could be potential targets for future melanoma therapeutics.
authors: Department of Dermatology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors: Lixia Z
authors: LZ
authors: Ellis
authors: Weimin
authors: W
authors: Liu
authors: Yuchun
authors: Y
authors: Luo
authors: Miyako
authors: M
authors: Okamoto
authors: Dovina
authors: D
authors: Qu
authors: Jeffrey H
authors: JH
authors: Dunn
authors: Mayumi
authors: M
authors: Fujita
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D059808:Polyphenols / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D053583:Interleukin-1beta; D059808:Polyphenols; D002392:Catechin; C045651:epigallocatechin gallate