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

Abstract 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‐κB 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. © 2002 Wiley‐Liss, Inc.