8-Chloro-Cyclic Adenosine Monophosphate is a Potent Inhibitor of Human Glioma Cell Proliferation In Vitro

Abstract

Cyclic adenosine 3′,5′-monophosphate (cAMP) is a second messenger playing an important role in cell growth and differentiation [1]. Since cAMP itself hardly enters the cell, the role of cAMP has been demonstrated by the use of cAMP analogs such as dibutyryl cAMP (dbcAMP). DbcAMP produces significant growth delay in multicellular spheroids derived from human brain tumours [2] and has also been found to induce morphological differentiation in human glioma cells [3]. However, usually the concentration of dbcAMP in these studies is very high (1 mM). Recently, cAMP analogs have been identified that selectively bind to one of the two known cAMP binding sites on the regulatory units of the cAMP dependent protein kinase (PKA). These site-selective analogs induce growth inhibition and differentiation in several human cancer cell lines at much lower concentrations than dbcAMP [1]. In the present study we compared the effects of the site-selective analog 8-chloro-cAMP (8ClcAMP) on human glioma cells to the effects of more commonly used cAMP analogs, such as dbcAMP.