Trans-resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways

G. Filomeni, I. Graziani, G. Rotilio, M. R. Ciriolo

Research output: Contribution to journalArticlepeer-review

Abstract

Polyphenols represent a large class of plant-derived molecules with a general chemical structure that act as potent free radical scavengers. They have long been recognized to possess several therapeutic activities ranging from anti-thrombotic to antioxidant. Moreover, the capability of polyphenols to act as reducing or oxidizing molecules depends on the presence of environmental metals and on the concentrations used. In this work we demonstrated that the stilbene trans-resveratrol was able to commit human breast cancer MCF-7 cells to apoptosis. Mainly, we evidenced a pivotal role of the mitochondria in this phenomenon as cytochrome c release into the cytosol was found after the treatment. We further showed that trans-resveratrol was able to affect cellular redox state. In particular, it induced an early production of ROS and lipid oxidation, and only later compromised the GSH/GSSG ratio. This mode of action was mirrored by a temporally different activation of JNK and P38MAPK, with the former rapidly induced and the latter weakly activated at long intervals. The results obtained demonstrate a pro-apoptotic activity for trans-resveratrol, and suggest a preferential activation of different classes of MAP kinases in response to different oxidative stimuli (ROS versus GSH/GSSG alteration).

Original languageEnglish
Pages (from-to)295-305
Number of pages11
JournalGenes and Nutrition
Volume2
Issue number3
DOIs
Publication statusPublished - Dec 2007

Keywords

  • Apoptosis
  • Glutathione
  • MAP kinases
  • Oxidative stress
  • Resveratrol
  • ROS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Genetics

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