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Histone deacetylase inhibitor 4-phenylbutyrate suppresses GAPDH mRNA expression in glioma cells.

Abstract
The histone deacetylase (HDAC) inhibitor 4-phenylbutyrate (4-PB) is a non-toxic compound that can induce differentiation and promote maturation of various types of malignant cells. In the present study we show that 4-PB inhibit glioma cell proliferation, induce apoptosis and decrease mRNA expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in a concentration-dependent manner. Proliferation of established rat glioma cell lines (RG2 and C6) in culture was significantly decreased after treatment with 4-PB (2-40 mM). Low concentrations of 4-PB (2-20 mM) induced cell differentiation followed by apoptosis, whereas higher concentrations of 4-PB (40 mM) induced cell necrosis. Also, low concentrations of 4-PB significantly decreased GAPDH mRNA expression in C6 and RG2 rat glioma cells, suggesting a link between decreased cell proliferation, energy consumption, and down-regulation of GAPDH gene expression. We have found that GAPDH mRNA expression is markedly increased in human glioblastoma tissues. Therefore, the novel effect of 4-PB described here may offer means to suppress growth of glioma cells by diminishing the key reaction in glycolysis as a therapeutic approach for cancer.
AuthorsI B Appelskog, O Ammerpohl, I G Svechnikova, W-O Lui, P M Almqvist, T J Ekström
JournalInternational journal of oncology (Int J Oncol) Vol. 24 Issue 6 Pg. 1419-25 (Jun 2004) ISSN: 1019-6439 [Print] Greece
PMID15138583 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Phenylbutyrates
  • RNA, Messenger
  • 4-phenylbutyric acid
  • Glyceraldehyde-3-Phosphate Dehydrogenases
Topics
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Brain Neoplasms (enzymology, pathology)
  • Cell Division (drug effects)
  • Down-Regulation
  • Enzyme Inhibitors (pharmacology)
  • Glioblastoma (enzymology, pathology)
  • Glyceraldehyde-3-Phosphate Dehydrogenases (genetics, metabolism)
  • Histone Deacetylase Inhibitors
  • Humans
  • Necrosis
  • Phenylbutyrates (pharmacology)
  • RNA, Messenger (metabolism)
  • Rats

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