Effect Of P38 MAPK On Elemene-induced Anti-proliferation And Cell Cycle Arrest In C6 Glioma Cells

Glioma, the most common brain tumors among the deadliest of human cancers, are highly invasive tumors, which respond poorly to chemotherapy and are impossible to be totally resected. Glioma can occur at any age and is generally incurable with a short median survival duration despite surgery, radiation therapy and chemotherapy. The treatment of glioma remains palliative for that no significant advancements in the treatment have developed in the past years.Elemene, extracted from the Chinese medicinal herb Curcuma wenyujin, is a mixture ofβ-,γ- andδ-elemene withβ-elemen as the main component and the other two as the lesser amounts. The anti-tumor effect of elemene has been proved in treatment of carcinomas of brain, liver, breast and other tissues as well as of leukemia in China. Recent studies showed that elemene could induce anti-proliferative effect in glioma cell lines. The mechanisms of elemene-induced anti-proliferation in glioma cell lines are still complex. Cellular behavior in response to extracellular stimuli is intervened by intracellular signaling pathways such as the mitogen-activated protein (MAP) kinase pathways.MAPK pathways are critical targets in gliomagenesis that regulate cellular proliferation, cell scatter and migration. JNK and p38 MAPK are major MAPK signaling pathways which are important in the control of cell proliferation, differentiation and apoptosis. Abundant evidence for p38 involvement in cell growth and cell cycle has been mentioned. The participation of p38 in cell growth has been observed in both yeast and mammals.In the studies outlined here, we investigated the mechanism of elemene-induced growth inhibition in rat C6 glioma cells in vitro and in vivo. We examined the effects of elemene on cell growth and cell cycle regulation in rat glioma cells and found that elemene dose- and time-dependently suppressed these cell growth. Treatment of C6 glioma cells with elemene, led to phosphorylation of p38 MAPK, cell cycle arrest inG0/G1 phase and inhibition of p38 MAPK blocked elemene-induced growth inhibition and cell cycle arrest of C6 cells. Moreover, elemene treatment also suppressed the tumor growth in C6 cell-transplanted tumors in nude mice. These data show a novel mechanism by which elemene inhibit glioma cell growth., suggest the therapeutic effect of elemene in treatment of glioma.