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Research Article
Silibinin down-regulates FAT10 and modulate TNF-α/IFN-γ-induced chromosomal instability and apoptosis sensitivity
Yun Gao, Steven Setiawan Theng, Way-Champ Mah, Caroline G. L. Lee
Biology Open 2015 4: 961-969; doi: 10.1242/bio.011189
Yun Gao
Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, 169610, Singapore
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  • For correspondence: bchleec@nus.edu.sg yugao2000@hotmail.com
Steven Setiawan Theng
NUS Graduate School of Integrative Sciences and Engineering, National University of Singapore, 119077, SingaporeDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 119077, Singapore
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Way-Champ Mah
Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, 169610, SingaporeNUS Graduate School of Integrative Sciences and Engineering, National University of Singapore, 119077, Singapore
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Caroline G. L. Lee
Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, 169610, SingaporeNUS Graduate School of Integrative Sciences and Engineering, National University of Singapore, 119077, SingaporeDepartment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 119077, SingaporeDuke-NUS Graduate Medical School Singapore, 169547, Singapore
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  • For correspondence: bchleec@nus.edu.sg yugao2000@hotmail.com
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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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Keywords

  • FAT10
  • Silibinin
  • TNF-α
  • IFN-γ
  • Chromosomal instability
  • Apoptosis

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Research Article
Silibinin down-regulates FAT10 and modulate TNF-α/IFN-γ-induced chromosomal instability and apoptosis sensitivity
Yun Gao, Steven Setiawan Theng, Way-Champ Mah, Caroline G. L. Lee
Biology Open 2015 4: 961-969; doi: 10.1242/bio.011189
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Research Article
Silibinin down-regulates FAT10 and modulate TNF-α/IFN-γ-induced chromosomal instability and apoptosis sensitivity
Yun Gao, Steven Setiawan Theng, Way-Champ Mah, Caroline G. L. Lee
Biology Open 2015 4: 961-969; doi: 10.1242/bio.011189

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