ABSTRACT
Pleiotropic pro-inflammatory cytokines, TNF-α and IFN-γ (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-κB 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-κB and STATs. As NF-κB 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-α-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-α-induced tumor growth.
Footnotes
↵* Present address: Center of Molecular Pathology, He University, Shenyang 110163, China.
↵‡ These authors contributed equally to this work
Competing interests
The authors declare no competing or financial interests.
Author contributions
C.G.L.L. and Y.G. conceived and designed the study; Y.G. and S.S.T. performed the experiments; Y.G., S.S.T. and W.-C.M. analyzed the data; Y.G., W.-C.M. and C.G.L.L. wrote the manuscript.
Funding
This work was supported by a grant from the National Medical Research Council (NMRC) [Grant number: NMRC/1306/2011] as well as block funding from the National Cancer Centre Singapore to C.G.L.L. and partially supported by a grant from National Nature Science Foundation of China [Grant number: 81102471] to Y.G.
Supplementary material
Supplementary material available online at http://bio.biologists.org/lookup/suppl/doi:10.1242/bio.011189/-/DC1
- Received December 10, 2014.
- Accepted April 28, 2015.
- © 2015. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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