Both Wheat (Triticum aestivum) Bran Arabinoxylans and Gut Flora-Mediated Fermentation Products Protect Human Colon Cells from Genotoxic Activities of 4-Hydroxynonenal and Hydrogen Peroxide

Abstract

Dietary fibers are fermented by the gut flora to yield short chain fatty acids (SCFAs), which inhibit the growth of tumor cells, induce glutathione S-transferases (GSTs), and protect cells from the genotoxic activity of 4-hydroxynonenal (HNE). Here, we investigated effects of wheat bran-derived arabinoxylans and fermentation products on these parameters of chemoprevention. Newly isolated water extractable (WeAx) and alkali extractable arabinoxylans (AeAx) were fermented under anaerobic conditions with human feces. Resulting fermentation supernatants (FSs) were analyzed for SCFAs and used to treat HT29 colon cancer cells. Cell growth, cytotoxicity, antigenotoxicity against hydrogen peroxide (H2O2) or HNE, and GST activity were determined. Nonfermented WeAx decreased H2O2-induced DNA damage by 64%, thus demonstrating chemoprotective properties by this nonfermented wheat bran fiber. The fermentation of WeAx and AeAx resulted in 3-fold increases of SCFA, but all FSs (including the control without arabinoxylans) inhibited the growth of the HT29 cells, reduced the genotoxicity of HNE, and enhanced the activity of GSTs (FS WeAx, 2-fold; FS AeAx, 1.7-fold; and control FS, 1.4-fold), which detoxify HNE. Thus, increases in SCFAs were not reflected by enhanced functional effects. The conclusion is that fermentation mixtures contain modulatory compounds that arise from the feces and might add to the effectiveness of SCFAs.

New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre?

“…Type 2 diabetes risk (662) ; risk of weight and fat gains; large bowel cancer (66,75,106,266) ; satiating effect; cholesterol, bile acids, hormonal activity; immune system, toxicant transit; production of SCFA in the colon (663) ; SCFA, growth of tumour cells, glutathione-S-transferase and genotoxic activity of 4-hydroxynonenal (664) ; dilution of gut substances; energy content and glycaemic index of foods; insulin response; free radicals (93) Insoluble fibre (63) : antioxidant-bound phenolics and colon (150) ; faecal wet and dry weight and faecal bulking effect (660) ; intestinal transit (660) (107,108) ; fat absorption (665) ; bile salt pool size (666) ; cholesterol turnover (667) ; formation of carcinogenic metabolites from bile salts (269) ; precursor of lignans (221) ; anti-carcinogenic (265) Oligosaccharides (raffinose, stachyose and fructans) (295) :…”

The formulation for cancer prevention & therapy

“…Nutritionally, they are classified under "unavailable carbohydrates" (dietary fiber) and are known to have beneficial effects in alleviating disease symptoms such as diabetes, atherosclerosis, and colon cancer [104]. Effects of wheat bran-derived arabinoxylans and fermentation products may act on chemoprevention [105].…”

Lipid Peroxidation in Colorectal Carcinogenesis: Bad and Good News

“…Comet assay demonstrated that HNE, at concentration higher than 150 μM, displays a genotoxic effect in the colon carcinoma cell line HT-29 (Glei et al, 2006;Ebert et al, 2001;Knoll et al, 2005) and in HT29clone19A, a permanently differentiated sub-clone treated with sodium butyrate (Augeron & Laboisse, 1984). Moreover, such high doses of HNE were able to affect DNA integrity in primary human colon cells (Schaferhenrich et al, 2003;Glei et al, 2007) and in LT97, an established cell line derived from a differentiated microadenoma, representing a model of an early premalignant genotype, carrying adenomatous polyposis coli (APC) and Ki-ras mutated, but normal p53 (Richter et al, 2002), three well-characterized genes involved in coloncancer progression (Fearon et al, 1990).…”

“…Similar results were obtained in HT-29 cells by using two wheat bran-derived arabinoxylans, fermented under anaerobic conditions in human feces. These two fermentation products inhibited growth and reduced the genotoxicity of HNE (100-200 μM) via up-regulation of the activity of GSTs, in absence of a GSTP1 or hGSTA4-4 increase (Glei et al, 2006). There is a growing interest in targeting aldose reductase (AR), as a novel therapeutic approach in preventing progression of colon cancer (Tammali et al, 2011).…”

“…Finally, as already mentioned, nutrients can modulate the HNE level in the colon, by affecting its metabolism. This is the case of fermented products of diet, such as butyrate (Knoll et al, 2005;Glei et al, 2006) and wheat bran-derived arabinoxylans, that can affect the HNE levels, by upregulating GSTs activities.…”