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.
Article Navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Other journals from The Company of Biologists
Seven things that shaped preLights in 2019
As 2020 gets well and truly underway, join us as we look back at seven things that shaped preLights in 2019. From launching preLists to getting nominated for an award, it was an exciting year!
Catch up with our first authors in the latest interviews. Meghan Barrett, Katherine Fiocca, Anand Singh, Hagen Gegner and Ling Wang discuss the implications of their research, life as an early-career researcher and their next steps.
Research by Gegner et al. uses targeted metabolomics and physiological measurements to explain the increased bleaching resistance of symbiotic Aiptasia exposed to high salinity.
Why publish with BiO?
Biology Open aims to provide rapid publication for scientifically sound observations and valid conclusions in developmental, cell, experimental and translational biology. Submit your paper for an easy and fast publication process. Recent disease modelling highlights in in BiO include work by Liu et al., which shows that zebrafish is a powerful in vivo model for investigating cardiomyopathy genetics.