Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis

Int J Cancer. 2002 Apr 10;98(5):761-9. doi: 10.1002/ijc.10202.


There is increasing evidence that food-derived polyphenols have a beneficial effect for cancers. Our purpose was to determine the effect and mechanism of action of these compounds on pancreatic cancer. We measured effects of quercetin on pancreatic cancer in a nude mouse model. We also investigated the effects of quercetin, rutin, trans-resveratrol and genistein on apoptosis and underlying signaling in pancreatic carcinoma cells in vitro. Quercetin decreased primary tumor growth, increased apoptosis and prevented metastasis in a model of pancreatic cancer. In vitro quercetin and trans-resveratrol, but not rutin, markedly enhanced apoptosis, causing mitochondrial depolarization and cytochrome c release followed by caspase-3 activation. In addition, the effect of a combination of quercetin and trans-resveratrol on mitochondrial cytochrome c release and caspase-3 activity was greater than the expected additive response. The inhibition of mitochondrial permeability transition prevented cytochrome c release, caspase-3 activation and apoptosis caused by polyphenols. Nuclear factor-kappa B activity was inhibited by quercetin and trans-resveratrol, but not genistein, indicating that this transcription factor is not the only mediator of the polyphenols' effects on apoptosis. The results suggest that food-derived polyphenols inhibit pancreatic cancer growth and prevent metastasis by inducing mitochondrial dysfunction, resulting in cytochrome c release, caspase activation and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Annexin A5 / metabolism
  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspase 3
  • Caspases / metabolism
  • Cyclosporine / pharmacology
  • Cytochrome c Group / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / therapeutic use*
  • Food
  • Immunoenzyme Techniques
  • Mice
  • Mice, Nude
  • Mitochondria / enzymology*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Phenols / therapeutic use*
  • Polymers / therapeutic use*
  • Transfection
  • Tumor Cells, Cultured


  • Annexin A5
  • Cytochrome c Group
  • Enzyme Inhibitors
  • Flavonoids
  • NF-kappa B
  • Phenols
  • Polymers
  • Cyclosporine
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases