The investigation of the anticancer effect of new sigma-1 receptor antagonist s1ra (E-52862) and rimcazole on the sphingosine kinase signal pathway in u87mg glioblastoma cells

Brain tumors are one of the dangerous and non-responsive solid tumours due to high invasiveness in the body. The aim of the study was to investigate the anticancer and antiproliferative effects of new selective sigma-1 receptor antagonist S1RA and sigma receptor antagonist rimcazole in a way as carring out followings; MTT and RT-CA DP assays, caspase-3 activation, Fluo-3 and Annexin/PI staining assays in flow cytometry and colony formation assay on Glioblastoma Multiforme cells (U87MG) that are highly metastatic, heterogenous and mortal. In addition to other assays mentioned above, RT-PCR (Real time polimerase chain reaction) measurements were carried out to evaluate the effects of S1RA ve rimcazole on sphingosine kinase pathway. According to the results, S1RA and rimkazol both caused antiproliferative and apoptotic effects at 24th hour in depending increasing concentrations that gave rise to inhibition of colony formation. S1RA was found more effective in % late apoptotic cell percentages whereas rimcazole was found more effective in early apoptotic cell percentages. S1RA caused significant caspase-3 activation in comparing with rimcazole. Both drugs' IC25 values have been shown to cause apparent increasing at intracellular cytosolic calcium levels. As to RT-PCR results, given the apoptotic effects, S1RA's IC50 concentration particularly caused downregulation on the target/reference ratios of mRNA expression of sphingosine kinase-1 and -2. In relation with carrying out this study, the evaluation of sigma receptor antagonists on glioblastoma will lead to new indicative pathways and new effective drugs in chemotherapy.