Anti-tumor effect of beta-elemene in glioblastoma cells depends on p38 MAPK activation.

beta-Elemene, a natural plant drug extracted from Curcuma wenyujin, has been used as an antitumor drug for different tumors, including glioblastoma. However, the mechanism of its anti-tumor effect is largely unknown. Here we report that anti-proliferation of glioblastoma cells induced by beta-elemene was dependent on p38 MAPK activation. Treatment of glioblastoma cell lines with beta-elemene, led to phosphorylation of p38 MAPK, cell-cycle arrest in G0/G1 phase and inhibition of proliferation of these cells. Inhibition of p38 MAPK reversed beta-elemene-mediated anti-proliferation effect. Furthermore, the growth of glioblastoma cell-transplanted tumors in nude mice was inhibited by intraperitoneal injection of beta-elemene. Taken together, our findings indicate that activation of p38 MAPK is critical for the anti-proliferation effect of beta-elemene and that p38 MAPK might be a putative pharmacological target for glioblastoma therapy.

[Influence of elemene on the expression of Bcl-2 family genes in rat C6 glioma cells].

OBJECTIVE: To observe the effects of elemene on the induction of apoptosis in rat C6 glioma cells and its influence on expression of Bcl-2 family genes. METHODS: Rat C6 glioma cells were cultured. Elemene of the concentrations of 0, 20, 40, 60, and 80 microg/ml were added for 12, 24, 36, 48, and 72 hours respectively. RT-PCR was used to detect the mRNA expression of Bcl-2/Bcl-x/1 genes. Western blotting was used to detect the protein expression of Bcl-2/Bcl-x/1 genes. The apoptosis of the cells was examined by flow cytometry. RESULTS: The cell counts of the 20, 40, 60, and 80 microg/ml elemene groups were 536 +/- 9, 375 +/- 10, 246 +/- 9, and 112 +/- 10/visual field respectively, all significantly lower than that of the 0 microg/ml elemene group (all F = 1292.416, P < 0.05) and the apoptotic rates of the 20, 40, 60, and 80 microg/ml elemene groups were (27 +/- 2)%, (29 +/- 4)%, (32 +/- 3)%, and (35 +/- 5)% respectively with an Ap peak. The protein expression of Bcl-2/Bcl-x/l genes was decreased in the elemene groups dose and time-dependently. The expression of Bax protein was decreased in the elemene groups too, however, not dose and time-dependently. CONCLUSION: Apoptosis caused by elemene may be associated with the down-regulation of Bcl-2/Bcl-x/l genes.

Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) is known to promote neuronal survival and differentiation and to guide axon extension both in vitro and in vivo. The BDNF-induced chemo-attraction of axonal growth cones requires Ca2+ signalling, but how Ca2+ is regulated by BDNF at the growth cone remains largely unclear. Extracellular application of BDNF triggers membrane currents resembling those through TRPC (transient receptor potential canonical) channels in rat pontine neurons and in Xenopus spinal neurons. Here, we report that in cultured cerebellar granule cells, TRPC channels contribute to the BDNF-induced elevation of Ca2+ at the growth cone and are required for BDNF-induced chemo-attractive turning. Several members of the TRPC family are highly expressed in these neurons, and both Ca2+ elevation and growth-cone turning induced by BDNF are abolished by pharmacological inhibition of TRPC channels, overexpression of a dominant-negative form of TRPC3 or TRPC6, or downregulation of TRPC3 expression via short interfering RNA. Thus, TRPC channel activity is essential for nerve-growth-cone guidance by BDNF.