Procyanidin B2 and a cocoa polyphenolic extract inhibit acrylamide-induced apoptosis in human Caco-2 cells by preventing oxidative stress and activation of JNK pathway

Ildefonso Rodriguez Ramiro, Sonia Ramos, Laura Bravo, Luis Goya, María Ángeles Martín

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128 Citations (Scopus)


Humans are exposed to dietary acrylamide (AA) during their lifetime; it is therefore necessary to investigate the mechanisms associated with AA induced toxic effects. Accumulating evidence indicates that oxidative stress may contribute to AA cytotoxicity, but the link between oxidative stress and AA cytotoxicity in the gastrointestinal tract, the primary organ in contact with dietary AA, has not been described. In this study, we evaluate the alterations of the redox balance induced by AA in Caco-2 intestinal cells as well as the potential protective role of natural antioxidants such as a well-standardized cocoa polyphenolic extract (CPE) and its main polyphenol components epicatechin (EC) and procyanidin B2 (PB2). We found that AA-induced oxidative stress in Caco-2 cells is evidenced by glutathione (GSH) depletion and reactive oxygen species (ROS) overproduction. AA also activated the extracellular-regulated kinases and the c-Jun N-amino terminal kinases (JNKs) leading to an increase in caspase-3 activity and cell death. Studies with appropriate inhibitors confirmed the implication of oxidative stress and JNKs activation in AA-induced apoptosis. Additionally, AA cytotoxicity was counteracted by CPE or PB2 by inhibiting GSH consumption and ROS generation, increasing the levels of gamma-glutamyl cysteine synthase and glutathione-S-transferase and blocking the apoptotic pathways activated by AA. Therefore, AA-induced cytotoxicity and apoptosis are closely related to oxidative stress in Caco-2 cells. Interestingly, natural dietary antioxidant such as PB2 and CPE were able to suppress AA toxicity by improving the redox status of Caco-2 cells and by blocking the apoptotic pathway activated by AA.
Original languageEnglish
Pages (from-to)1186-1194
Number of pages9
JournalJournal of Nutritional Biochemistry
Issue number12
Publication statusPublished - Dec 2011


  • Flavonoids
  • Apoptosis
  • Polyphenols
  • Cacao
  • Glutathione
  • Humans
  • Plant Extracts
  • Caco-2 Cells
  • Catechin
  • Biflavonoids
  • Acrylamide
  • Proanthocyanidins
  • JNK Mitogen-Activated Protein Kinases
  • Cell Death
  • Oxidative Stress
  • Signal Transduction
  • Epicatechin
  • ROS
  • Signalling pathways

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