Red meat and colorectal cancer: Nrf2-dependent antioxidant response contributes to the resistance of preneoplastic colon cells to fecal water of hemoglobin- and beef-fed rats

This study demonstrated that fecal water of hemoglobin- and beef-fed rats preferentially induced apoptosis in mouse normal colon epithelial cells than in those carrying mutation on Apc (Adenomatous polyposis coli) gene, considered as preneoplastic. Highlighting the importance of lipid peroxidation and neoformation of secondary aldehydes like 4-hydroxy-2-nonenal (HNE), we optimized the depletion of carbonyl compounds in the fecal water which turned out to abolish the differential apoptosis in both cell lines. To explain the resistance of preneoplastic cells towards fecal water toxicity, we focused on Nrf2, known to be activated by aldehydes, including HNE. Fecal water activated Nrf2 in both cell lines, associated with the induction of Nrf2-target genes related to aldehydes detoxification. However, the antioxidant defense appeared to be higher in preneoplastic cells, favoring their survival, as evidenced by Nrf2 inactivation. Taken together, our results suggest that Nrf2-dependent antioxidant response was involved in the resistance of preneoplastic cells upon exposure to fecal water of hemoglobin- and beef-fed rats. This difference could explain the promoting effect of red meat and heme-enriched diet on colorectal cancer, by initiating positive selection of preneoplastic cells.

Source: Carcinogenesis - May 22, 2016 Category: Cancer & Oncology Authors: Surya, R., Helies-Toussaint, C., Martin, O. C., Gauthier, T., Gueraud, F., Tache, S., Naud, N., Jouanin, I., Chantelauze, C., Durand, D., Joly, C., Pujos-Guillot, E., Pierre, F. H., Huc, L. Tags: Original Manuscript Source Type: research