Tumor Biology

, Volume 36, Issue 11, pp 9067–9072 | Cite as

Specific combinations of the chromatin-modifying enzyme modulators significantly attenuate glioblastoma cell proliferation and viability while exerting minimal effect on normal adult stem cells growth

Research Article

Abstract

The discoveries of recent decade showed that all critical changes in cancer cells, such as silencing of tumor-suppressor genes and activation of oncogenes, are caused not only by genetic but also by epigenetic mechanisms. Although epigenetic changes are somatically heritable, in contrast to genetic changes, they are potentially reversible, making them good targets for therapeutic intervention. Covalent modifications of chromatin such as methylation and acetylation of histones and methylation of DNA are the important components of epigenetic machinery. In this study, we investigated the effect of different modulators of DNA and histone covalent-modifying enzymes on the proliferation and viability of normal adult stem cells, such as human bone marrow mesenchymal stem cells (hMSCs), and on malignant tumor cells, such as glioblastoma (GB) D54 cells. Results demonstrated that specific combinations of histone methyltransferases and deacetylases inhibitors significantly attenuated D54 cells viability but having only a small effect on hMSCs growth. Taken together, these studies suggest that specific combinations of histone covalent modifiers could be an effective treatment option for the most aggressive type of primary brain tumors such as glioblastoma multiforme.

Keywords

Epigenetic Chromatin DNA methylation Glioblastoma Stem cells 

Notes

Acknowledgments

This work was supported by VA Medical Research, Fraternal Order of Eagles, and by the Women’s Health Research Program, Falk Medical Research Trust and Frank L. Weyenberg Charitable Trust at the Medical College of Wisconsin. We thank Dr. Bigner for providing us with D-54MG and Kyle Stehlik for technical assistance.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Cell Reprogramming & Therapeutics LLCWaukeshaUSA
  2. 2.Department of Obstetrics and GynecologyMedical College of WisconsinMilwaukeeUSA
  3. 3.Department of Pharmacology and ToxicologyMedical College of WisconsinMilwaukeeUSA

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