Cyclic AMP-dependent regulation of differentiation of rat C6 glioma cells by panaxydol

Abstract

Objectives: Preliminary works have indicated that panaxydol possesses growth inhibition and induces differentiation in rat C6 glioma cells. However, the molecular mechanism underlying this differentiation remains unknown. We sought to investigate the role of cyclic adenosine monophosphate (cAMP) in cellular differentiation induced by panaxydol.Methods: C6 cells were treated with panaxydol and various specific inhibitors, and the inhibition of cell growth was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay and homotransplantation in nude mice. Astrocytic processes were quantified under a phase-contrasted microscope. Glial fibrillary acidic protein expression and cell migration were carried out by Western blot and scratch-wound test, respectively. In addition, the intracellular cAMP concentration was measured by immunoassay.Results: Panaxydol induces the elevation of intracellular cAMP concentration in C6 cells. The effects of growth inhibition in vitro and in vivo and induction of differentiation in C6 cells by panaxydol could be inhibited by the cAMP inhibitor, Rp-adenosine 3′,5′-cyclic monophosphothioate, but not by protein kinase A or protein kinase C specific inhibitors.Conclusion: These results suggest that the cAMP-dependent pathway may regulate cellular proliferation, migration and differentiation in C6 glioma cells by panaxydol.