Abstract |
3-Hydroxiglutaric acid (3-OH-GA) is a disease-specific metabolite that accumulates in tissues and body fluids of patients with Glutaric aciduria type I (GAI) and has been associated with vascular abnormalities in these kindreds. Here, we demonstrate that 3-OH-GA also affects the integrity of tumor vessels leading to tumor growth inhibition in a subcutaneous model of human glioblastoma multiforme (GBM). This effect correlated with a marked decrease of VE-Cadherin expression in endothelium of 3-OH-GA-treated tumors. Furthermore, in vitro observations indicated also a direct effect of 3-OH-GA in glioma cells that showed defective mitosis and significant proliferation inhibition. In summary, the GAI-specific metabolite 3-OH-GA significantly inhibited growth of GBM xenografts by affecting the structural integrity of tumor blood vessels and in addition by causing defective mitosis and proliferation inhibition of tumor cells.
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Authors | Leticia Oliveira-Ferrer, Jasmin Wellbrock, Melanie Braig, Marianne Klokow, Jessica Hauschild, Carsten Bokemeyer, Walter Fiedler, Suleyman Ergun, Gunter Schuch |
Journal | Cancer letters
(Cancer Lett)
Vol. 326
Issue 2
Pg. 161-7
(Dec 30 2012)
ISSN: 1872-7980 [Electronic] Ireland |
PMID | 22902505
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- 3-hydroxyglutaric acid
- DNA, Complementary
- Glutarates
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Topics |
- Animals
- Blood Vessels
(drug effects)
- Cell Division
(drug effects)
- Cell Line, Tumor
- DNA, Complementary
- Glioblastoma
(blood supply, pathology)
- Glutarates
(pharmacology)
- Humans
- Immunohistochemistry
- Mice
- Mice, Nude
- Neovascularization, Pathologic
- Oligonucleotide Array Sequence Analysis
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