We found that osthole and TRAIL alone, had no effect on apoptosis, but combined treatment with osthole and TRAIL markedly induced apoptosis in Caki (renal carcinoma), U251MG (glioma) and MDA-MB-231 (breast carcinoma) cells.
Finally, MSCs expressing TRAIL improved the median survival of irradiated mice bearing intracranial U87 glioma xenografts in comparison with nonirradiated and irradiated control mice.
Inhibition of either PPARgamma or MEK1/2 blocked the Troglitazone-mediated phosphorylation of BAD and further increased the synergistic induction of glioma cell death by TRAIL and Troglitazone.
Novel therapeutic approaches using TRAIL or agonistic TRAIL receptor antibodies in combination with proteasome inhibitors may represent a promising approach to reactivate apoptosis in therapy-resistant high-grade gliomas.
The results of the present study show that the anti-diabetic drug troglitazone sensitizes human glioma and neuroblastoma cells to TRAIL-induced apoptosis.
Roles of tyrosine phosphorylation and cleavage of protein kinase Cdelta in its protective effect against tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis.
Moreover, Ad-Apo2L/TRAIL gene transfer inhibits soluble His-tagged Apo2L/TRAIL-induced apoptosis, strongly suggesting that the adenovirally encoded full-length Apo2L/TRAIL is not a suitable molecule for glioma cancer gene therapy.
Taken together, these findings suggest that resistance to TRAIL by lack of TRAIL receptors on glioma is restored by genotoxic agents, which support the new strategies for tumour killing by TRAIL-bearing cytotoxic cells in combination with genotoxic treatment.
The authors first examined sensitivity to TRAIL and expression of TRAIL receptors in four established and four primary cultured glioma cell lines by using viability and fluorescent apoptosis assays.
We analyzed the expression of TRAIL and its receptors in a panel of human brain tumors (n = 34) and in four glioma cell lines in comparison to normal brain tissue.