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Valproic acid inhibits angiogenesis in vitro and glioma angiogenesis in vivo in the brain.
- Source :
-
Neurologia medico-chirurgica [Neurol Med Chir (Tokyo)] 2012; Vol. 52 (4), pp. 186-93. - Publication Year :
- 2012
-
Abstract
- Antiangiogenic strategy is promising for malignant glioma. Histone deacetylase inhibitors (HDACIs) are unique anticancer agents that exhibit antiangiogenic effects. The in vitro and in vivo antiangiogenic effects of HDACIs, valproic acid (VPA), were investigated in malignant glioma in the brain. In vitro, VPA preferentially inhibited endothelial cell proliferation compared to glioma cell proliferation at the optimum concentration in a dose-dependent manner. VPA reduced vascular endothelial growth factor (VEGF) secretion of glioma cells in a dose-dependent manner under both normoxic and hypoxic conditions. VPA was also found to inhibit tube formation in the angiogenesis assay. In vivo, treatment with VPA combined with irinotecan reduced the number of vessels expressing factor VIII in the brain tumor model. VPA inhibits glioma angiogenesis by direct (inhibition of endothelial cell proliferation and tube formation) and indirect (decreased secretion of VEGF by glioma cells) mechanisms. These data suggest a potential role for VPA as an adjuvant therapy for patients with malignant glioma.
- Subjects :
- Angiogenesis Inhibitors therapeutic use
Animals
Anticonvulsants pharmacology
Anticonvulsants therapeutic use
Antineoplastic Agents therapeutic use
Brain Neoplasms blood supply
Brain Neoplasms physiopathology
Cell Line, Transformed
Cell Line, Tumor
Female
Glioma blood
Glioma physiopathology
Humans
Neoplasms, Experimental blood supply
Neoplasms, Experimental drug therapy
Neoplasms, Experimental physiopathology
Neovascularization, Pathologic physiopathology
Neovascularization, Pathologic prevention & control
Rats
Rats, Wistar
Valproic Acid therapeutic use
Angiogenesis Inhibitors pharmacology
Antineoplastic Agents pharmacology
Brain Neoplasms drug therapy
Glioma drug therapy
Neovascularization, Pathologic drug therapy
Valproic Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1349-8029
- Volume :
- 52
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neurologia medico-chirurgica
- Publication Type :
- Academic Journal
- Accession number :
- 22522328
- Full Text :
- https://doi.org/10.2176/nmc.52.186