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

J Exp Ther Oncol. 2005;5(1):39-48.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Mitochondria / enzymology*
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / genetics*


  • 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