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.
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Authors | I B Appelskog, O Ammerpohl, I G Svechnikova, W-O Lui, P M Almqvist, T J Ekström |
Journal | International journal of oncology
(Int J Oncol)
Vol. 24
Issue 6
Pg. 1419-25
(Jun 2004)
ISSN: 1019-6439 [Print] Greece |
PMID | 15138583
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Enzyme Inhibitors
- Histone Deacetylase Inhibitors
- Phenylbutyrates
- RNA, Messenger
- 4-phenylbutyric acid
- Glyceraldehyde-3-Phosphate Dehydrogenases
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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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