Silibinin down-regulates FAT10 and modulate TNF-?/IFN-?-induced chromosomal instability and apoptosis sensitivity.

ABSTRACT: Pleiotropic pro-inflammatory cytokines, TNF-? and IFN-? (TI), play important yet diverse roles in cell survival, proliferation, and death. Recent evidence highlights FAT10 as a downstream molecule in the pathway of inflammation-induced tumorigenesis through mediating the effect of cytokines in causing numerical CIN and protecting cells from cytokines-induced cell death. cDNA microarray analysis of cells treated with TI revealed 493 deregulated genes with FAT10 being the most up-regulated (85.7-fold) gene and NF-?B being the key nodal hub of TI-response genes. Silibinin is reported to be a powerful antioxidant and has anti-C effects against various carcinomas by affecting various signaling molecules/pathways including MAPK, NF-?B and STATs. As NF-?B signaling pathway is a major mediator of the tumor-promoting activities of TI, we thus examine the effects of silibinin on TI-induced FAT10 expression and CIN. Our data showed that silibinin inhibited expression of FAT10, TI-induced chromosome instability (CIN) as well as sensitizes cells to TI-induced apoptosis. Significantly, silibinin suppressed intra-tumorally injected TNF-?-induced tumor growth. This represents the first report associating silibinin with FAT10 and demonstrating that silibinin can modulate TI-induced CIN, apoptosis sensitivity and suppressing TNF-?-induced tumor growth.

SUBMITTER: Gao Y 

PROVIDER: S-EPMC4542280 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature