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 differe ntiation 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 effective ly. 8-CI-cAMP and tiazofurin (TR) are site-specific analogs that selectivel y inhibit PKAI and IMP dehydrogenase, are directly involved in cell prolife ration and apoptosis, and mediate the mitogenic effects of different oncoge nes and growth factors. In this study, we have examined influence of 8-CI-c AMP 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-linke d immunoassay and GFAP immunocytochemistry we demonstrated the effects of t hese compounds. Our results demonstrate that 8-CI-cAMP and TR decrease VEGF production by U251 MG cells, and that under the influence of both agents t hese cells increase GFAP expression and change their morphology, becoming m ore differentiated. These findings also suggest that 8-CI-cAMP and TR may h ave potential for further investigation of their antiangiogenic and differe ntiational role in malignant disease such as human gliomas. [(C) 2000 Lippi ncott Williams & Wilkins].