The role of natural food products in prevention of cancer has been confirmed in several epidemiological studies; however, the mechanism of chemoprevention by the dietary constituents largely remains unknown. Curcumin, the yellow pigment and active component of the spice turmeric (Curcuma longa) exhibits chemopreventive and growth inhibitory activity against several tumor lines. The human malignant glioma cell line U87 is only slightly susceptible to tumor necrosis factor related apoptosis-inducing ligent (TRAIL), a member of the tumor necrosis factor family of cell death-inducing ligands or curcumin alone at low concentrations. In this study, we investigated whether curcumin and TRAIL cooperatively interact to promote death of U87 cells. At low concentrations (20μM curcumin and 5ng/ml TRAIL), neither of the two agents alone produced significant cytotoxicity in U87 cells, as measured by MTS dye reduction assay. On the other hand, cell death was markedly enhanced if tumor cells were treated with curcumin and TRAIL together. The combined curcumin and TRAIL treatment increased the number of hypodiploid cells in sub-G1 phase and induced DNA fragmentation in U87 cells. The combined treatment induced cleavage of procaspases-3, -8, and -9, truncation of Bid, and the release of cytochrome c from mitochondria. These data indicate that both the extrinsic (receptor- mediated) and intrinsic (chemical-induced) pathways of apoptosis are triggered in U87 cells treated with combination of curcumin and TRAIL. These results define a potentional use of curcumin to sensitize glioma cells for TRAIL-mediated immunotherapy.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]