Curcumin differentially sensitizes malignant glioma cells to TRAIL/Apo2L-mediated apoptosis through activation of procaspases and release of cytochrome c from mitochondria.

Abstract

Malignant glioma cells are generally resistant or only weakly sensitive to tumor necrosis factor family of cell death-inducing ligands, including TNF-related apoptosis-inducing ligand (TRAIL)/Apo2L. The chemopreventive activity of polyphenolic compounds present in plant-derived food products has been well recognized in epidemiological studies; however, the mechanism of chemoprevention by these dietary constituents largely remains unknown. Curcumin, the yellow pigment in the spice turmeric, has profound anti-inflammatory activity and exhibits chemopreventive and tumor growth inhibitory activity. In the present study, we investigated whether curcumin sensitizes malignant glioma cell lines U251MG and U87MG to TRAIL-induced apoptosis. Treatment with low concentrations (5-20 microM) of curcumin alone had no effect on the viability of either cell line. At low concentration (5 ng/ml) TRAIL induced cytotoxicity in U251MG cells but not in U87MG cells. Whereas curcumin at subtoxic concentration sensitized U87MG cells to TRAIL-induced cytotoxicity, it had no effect on TRAIL-mediated cytotoxicity in U251MG cells. The combined curcumin and TRAIL treatment enhanced accumulation of hypo-diploid U87MG cells in sub G1 cell cycle phase and induced the cleavage of procaspases-3, -8, -9 and release of cytochrome c from mitochondria. These data indicate that curcumin differentially sensitizes glioma cells to TRAIL-induced apoptosis through the activation of both extrinsic (receptor-mediated) and intrinsic (chemical-induced) pathways of apoptosis. These results define a potential use of curcumin to sensitize glioma cells for TRAIL-mediated immunotherapy.

• Authors: Xiaohua Gao, Dorrah Deeb, Hao Jiang, Yong B Liu, Scott A Dulchavsky, Subhash C Gautam
• Journal: Journal of experimental therapeutics & oncology (J Exp Ther Oncol) Vol. 5 Issue 1 Pg. 39-48 ( 2005) ISSN: 1359-4117 [Print] United States
• PMID: 16416600 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• Indicators and Reagents
• Membrane Glycoproteins
• TNF-Related Apoptosis-Inducing Ligand
• TNFSF10 protein, human
• Tumor Necrosis Factor-alpha
• Cytochromes c
• L-Lactate Dehydrogenase
• CASP3 protein, human
• CASP8 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 8
• Caspase 9
• Caspases
• Curcumin

Topics

• Antineoplastic Agents
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics)
• Blotting, Western
• Brain Neoplasms (pathology)
• Caspase 3
• Caspase 8
• Caspase 9
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Curcumin
• Cytochromes c (metabolism)
• Enzyme Activation
• Glioma (pathology)
• Humans
• Indicators and Reagents
• L-Lactate Dehydrogenase (metabolism)
• Membrane Glycoproteins (genetics)
• Mitochondria (drug effects, enzymology)
• TNF-Related Apoptosis-Inducing Ligand
• Tumor Necrosis Factor-alpha (genetics)