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. Tumour Biol 2015 Nov;36(11):9067-72
Date
06/19/2015Pubmed ID
26084611DOI
10.1007/s13277-015-3654-1Scopus ID
2-s2.0-84949109374 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
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.
Author List
Alexanian AR, Huang YWAuthor
Arshak R. Alexanian VMD, PhD Adjunct Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adult Stem CellsBone Marrow Cells
Cell Proliferation
Cell Survival
Chromatin
DNA Methylation
Epigenesis, Genetic
Glioblastoma
Histone Deacetylase Inhibitors
Histone Deacetylases
Histone-Lysine N-Methyltransferase
Histones
Humans