Inhibition of glioma cell viability by jatrophone via NF-κB down-regulation and apoptosis inhibitor up-regulation

Abstract

IntroductionThe present study evaluated the pro-survival signaling pathway inhibition potential of jatrophone in glioblastoma cells with the intention to develop effective treatment for glioblastoma.Material and methodsChanges in proliferation of cells were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological changes were evaluated by electron microscopy and apoptosis by flow cytometry.ResultsThe proliferative potential of glioma cells showed significant reduction on treatment with jatrophone. The shrinkage and detachment from the flask surface was prominent in glioma cells on treatment with 15 µM jatrophone. Treatment with jatrophone (4.8 µM) for 72 h increased apoptosis in U87MG and A172 cells. The immunocytochemistry showed a significant decrease in the level of intracellular NF-B p65 in glioma cells on treatment with jatrophone. Jatrophone treatment significantly suppressed nuclear NF-B p65/total NF-B p65 in glioma cells. Treatment with jatrophone suppressed levels of survivin, XIAP and Bcl-2 in glioma cells relative to control. The Bax level in glioma cells was enhanced markedly relative to control on treatment with jatrophone. Activation of caspase-9 and -3 in glioma cells was markedly increased on treatment with jatrophone.ConclusionsJatrophone acts as inhibitory agent for glioblastoma cell proliferation and mediator of apoptosis. Therefore, jatrophone can be used as a therapeutic agent for glioblastoma treatment.