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Stem Cell Reviews and Reports

, Volume 10, Issue 1, pp 103–113 | Cite as

Sirtuin-2 Activity is Required for Glioma Stem Cell Proliferation Arrest but not Necrosis Induced by Resveratrol

  • Salwa Sayd
  • Cécile Thirant
  • Elias A. El-Habr
  • Joanna Lipecka
  • Luiz Gustavo Dubois
  • Alexandra Bogeas
  • Nadia Tahiri-Jouti
  • Hervé ChneiweissEmail author
  • Marie-Pierre JunierEmail author
Article

Abstract

Glioblastomas, the most common form of primary brain tumors, are the fourth cause of death by cancer in adults. Increasing evidences suggest that glioblastoma resistance to existing radio- and chemotherapies rely on glioblastoma stem cells (GSCs). GSCs are endowed with a unique combination of stem-like properties alike to normal neural stem cells (NSCs), and of tumor initiating properties. The natural polyphenol resveratrol is known to exert opposite actions on neural cells according to their normal or cancerous status. Here, we used resveratrol to explore the molecular mechanisms differing between GSCs and NSCs. We observed a dual action of resveratrol on GSCs: resveratrol blocked GSC proliferation up to 150 μM and induced their necrosis at higher doses. On the opposite, resveratrol had no effect on NSC behavior. To determine the mechanisms underlying resveratrol effects, we focused our attention on the family of NAD-dependent deacetylases sirtuins (SIRT). A member of this family, SIRT1, has been repetitively shown to constitute a preferential resveratrol target, at least in normal cells. Western blot analysis showed that SIRT1 and SIRT3 were expressed by both GSCs and NSCs whereas SIRT2 expression was restricted to GSCs. Pharmacological blockade of SIRT2 activity or down-regulation of SIRT2 expression with siRNAs counteracted the inhibitory effect of resveratrol on cell proliferation. On the contrary, inhibition of SIRT2 activity or expression did not counteract GSC necrosis observed in presence of high doses of resveratrol. Our results highlight SIRT2 as a novel target for altering GSC properties.

Keywords

Sirtuin Cancer stem cell α-tubulin Necrosis 

Notes

Acknowledgments

The authors thank Amélia Dias-Morais for excellent technical assistance, and are grateful to Dr P. Auberger (INSERM U895, Nice, France) for providing LC3 siRNA. This work was supported by ARC and by Région Ile de France-Canceropôle (CT and EAE fellowships), and by CAPES/COFECUB (LGD and AB fellowships).

Conflict of Interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Salwa Sayd
    • 1
    • 2
  • Cécile Thirant
    • 1
    • 3
  • Elias A. El-Habr
    • 1
  • Joanna Lipecka
    • 1
  • Luiz Gustavo Dubois
    • 1
  • Alexandra Bogeas
    • 1
  • Nadia Tahiri-Jouti
    • 2
  • Hervé Chneiweiss
    • 1
    • 4
    Email author
  • Marie-Pierre Junier
    • 1
    • 4
    Email author
  1. 1.Team Glial Plasticity, U894 Inserm, Université Paris DescartesParisFrance
  2. 2.Laboratory of Genetics and Molecular Pathology, Faculty of Medicine and Pharmacy of CasablancaCasablancaMorocco
  3. 3.U1009 Inserm IGR Université Paris-XIVillejuifFrance
  4. 4.U894 Team Glial Plasticity, Center of Psychiatry and NeurosciencesParisFrance

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