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

Abstract

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 (ERKs) 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 (γ-GCS) and glutathione-S-transferase (GST) 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.3

The protective effect of N-acetylcysteine against acrylamide toxicity in liver and small and large intestine tissues

“…Studies in which acrylamide was added to the cell culture medium, the oxidant parameters increased and cell damage appeared. These fi ndings support our study (55,56,(61)(62)(63).…”

Dietary flavanols exert different effects on antioxidant defenses and apoptosis/proliferation in Caco-2 and SW480 colon cancer cells

“…In line with this potential mechanism of action, it has been shown that in Caco-2 cells PB2 increases the activity of antioxidant/detoxification enzymes, ECG increases the activity of GPx and EC does not affect to any activity of the protective GSHdependent enzymes (Rodríguez-Ramiro et al, 2010. In the present study ECG evokes a substantial increase in GPx activity without altering GR and GST activities in SW480 cells.…”

“…This proliferative effect could be related to the activation of key proteins in survival/proliferation pathways, since the selective blockage of the PI-3-kinase and ERK pathways by pharmacological inhibitors suppressed PB2-induced proliferation in SW480 cells, as previously shown for EC (GranadoSerrano et al, 2007). In line with this, it has been recently demonstrated that PB2 exerted a protective role against an induced oxidative stress in Caco-2 cells (Rodríguez-Ramiro et al, 2010. In addition, cellular survival seemed to depend on the induction of the ERK pathway in…”

“…Moreover, it should be highlighted that the loss of cellular GSH redox status seems to be an important player in apoptotic signaling (Granado-Serrano et al, 2009b;Rodríguez-Ramiro et al, 2010).…”

Downregulated Lipid Metabolism in Differentiated Murine Adipocytes by Procyanidins from Defatted Grape Seed Meal

“…Proanthocyanidins, which are abundant from various natural sources such as apples, 1) cranberries, 2) jujube (Ziziphus jujuba) fruits, 3) cinnamon, 4) sorghum, 5) and cocoa, 6,7) are known to have beneficial effects on health: anti-tumorial, 5,8,9) anti-inflammatory, 10,11) neuroprotective, 12) hypotensive or vasorelaxant, [13][14][15] and cardioprotective. 16) An antioxidative function is believed to be a common characteristic of proanthocyanidins which enables these chemopreventive effects.…”