8-Cl-cAMP and tiazofurin affect vascular endothelial growth factor production and glial fibrillary acidic protein expression in human glioblastoma cells.
Compounds that could block tumor angiogenesis and induce tumor cell differentiation in malignant gliomas represent a very valuable tool in anticancer treatments. In this paper, we demonstrate that more selective drugs, which interfere with specific cellular targets, could treat glioma more effectively. 8-Cl-cAMP and tiazofurin (TR) are site-specific analogs that selectively inhibit PKAI and IMP dehydrogenase, are directly involved in cell proliferation and apoptosis, and mediate the mitogenic effects of different oncogenes and growth factors. In this study, we have examined influence of 8-Cl-cAMP and TR on the production of an angiogenic factor [vascular endothelial growth factor (VEGF)] by human glioblastoma U251 MG cells, as well as their influence on the expression of a differentiating marker [glial fibrillary acidic protein (GFAP)]. Using a cell proliferation assay, VEGF enzyme-linked immunoassay and GFAP immunocytochemistry we demonstrated the effects of these compounds. Our results demonstrate that 8-Cl-cAMP and TR decrease VEGF production by U251 MG cells, and that under the influence of both agents these cells increase GFAP expression and change their morphology, becoming more differentiated. These findings also suggest that 8-Cl-cAMP and TR may have potential for further investigation of their antiangiogenic and differentiational role in malignant disease such as human gliomas.
Drabek
K
K
Institute for Biological Research, Department of Neurobiology and Immunology, Belgrade, Yugoslavia.
Pesić
M
M
Piperski
V
V
Ruzdijić
S
S
Medić-Mijacević
L
L
Pietrzkowski
Z
Z
Rakić
L
L
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis* / Q000378:metabolism; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D005904:Glial Fibrillary Acidic Protein; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012254:Ribavirin; C044258:8-chloro-cyclic adenosine monophosphate; C033706:tiazofurin