Colorectal cancer is the third most diagnosed cancer worldwide and linked to dietary/lifestyle factors. Arthrospira (Spirulina) platensis (AP) contains bioactive compounds with beneficial effects in vivo/in vitro. We evaluated the effects of AP feeding against 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Male Sprague Dawley rats were given subcutaneous injections of DMH (4 × 40 mg/kg body weight) (G1–G3) or vehicle (G4–G5) twice a week (weeks 3–4). During weeks 1–4, animals were fed a diet containing 1 % (G2) or 2 % (G3–G4) AP powder (w/w). After this period, all groups received a balanced diet until week 12. Some animals were euthanised after the last DMH injection (week 4) for histological, immunohistochemical (Ki-67, γ-H2AX and caspase-3) and molecular analyses (real time-PCR for 91 genes), while other animals were euthanised at week 12 for preneoplastic aberrant crypt foci (ACF) analysis. Both AP treatments (G2–G3) significantly decreased the DMH-induced increase in γ-H2AX (DNA damage) and caspase 3 (DNA damage-induced cell death) in colonic crypts at week 4. In addition, Cyp2e1 (Drug metabolism), Notch1, Notch2 and Jag1 genes (Notch pathway) and Atm, Wee1, Chek2, Mgmt, Ogg1 and Xrcc6 genes (DNA repair) were also down-regulated by 2 % AP feeding (G3) at week 4. A significant reduction in ACF development was observed in both AP-treated groups (G2–G3) at week 12. In conclusion, findings indicate that AP feeding reduced acute colonic damage after DMH, resulting in fewer preneoplastic lesions. Our study provided mechanistic insights on dietary AP-preventive effects against early colon carcinogenesis.

The development of colorectal cancer involves some morphological changes, and in the initial stage, pre-neoplastic lesions called aberrant crypt foci (ACF) appear. Thus, an intervention with sources of bioactive compounds such as Hibiscus sabdariffa L., rich in phenolic compounds and anthocyanins, could attenuate the risk of developing these lesions due to its antioxidant, anti-inflammatory and anti-proliferative properties. Therefore, the aim of this study was to evaluate the effects of 5 % and 10 % supplementation of dehydrated H. sabdariffa calyces (DHSC) during the development of 1,2-dimethylhydrazine-induced pre-neoplastic lesions in male BALB/c mice. The characterisation of DHSC was carried out. The in vivo experiment lasted 12 weeks, and the animals were randomly divided into three experimental groups: the control group (CON) and the supplemented groups with 5 % DHSC and 10 % DHSC. The activities of liver enzymes catalase (CAT) and superoxide dismutase were determined. In addition, ACF, SCFA, presence of inflammatory infiltrates, goblet cells and leucocytes in the colonic mucosa were quantified. There was a significant reduction in ACF and the presence of inflammatory infiltrates in the colon of animals in groups 5DHSC and 10DHSC. In addition, the 10DHSC group showed an increase in the activity of the CAT enzyme, in the production of butyrate and in the presence of natural killer cells in the colon, in addition to more hypertrophied goblet cells. Based on these findings, it is suggested that DHSC supplementation may be recommended to attenuate cellular responses in the early stage of pre-neoplastic lesions.

Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown to modulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.

The present study aimed to explore the role(s) of the soya isoflavone genistein (GEN) in preventing the development of colon pre-neoplasia, using Wingless/int (WNT)/β-catenin as a molecular marker of colon abnormality. Specifically, the effects on the WNT/β-catenin signalling pathway from GEN were examined by using an azoxymethane (AOM)-induced rat colon cancer model. Male Sprague–Dawley rats were fed a control (CTL), a soya protein isolate (SPI) or a GEN diet from gestation to 13 weeks of age. The first sampling was conducted at 7 weeks of age for pre-AOM analysis. The remaining rats were injected with AOM at 7 weeks of age. The descending colon was collected 6 weeks later for the evaluation of aberrant crypt foci (ACF), gene expression and nuclear protein accumulation. AOM injection induced aberrant nuclear accumulation of β-catenin in the CTL group but not in the SPI or GEN group. Moreover, the WNT target genes Cyclin D1 and c-Myc were repressed by SPI and GEN. Meanwhile, SPI and GEN suppressed the expression of WNT signalling genes including Wnt5a, Sfrp1, Sfrp2 and Sfrp5 to the similar level to that of the pre-AOM period. Rats fed SPI and GEN had a decreased number of total aberrant crypts. GEN feeding also resulted in a reduced number of ACF with N = 3 per foci. The reduction of WNT/β-catenin signalling was correlated with the decrease in total aberrant crypts. By testing WNT/β-catenin signalling as a biomarker of colon carcinogenic potential, we showed the novel role of GEN as a suppressor of carcinogen-induced WNT/β-catenin signalling in preventing the development of early colon neoplasia.

Many epidemiological and experimental studies have suggested an important role for dietary fibre (DF) of cereals in the prevention of colon cancer. The objective of the present study was to explain the effects of the DF of barley Rihane (BR) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) and colonic bacterial diversity in rats. Following an acclimatisation period, rats were divided into four groups and fed a control (C) diet or experimental diet containing 30 % of BR. DF content in the experimental diet was twice that of the C diet (total DF was 8·69 % in the C diet and 15·24 % in the BR diet). At 7 and 8 weeks of age, rats received two successive subcutaneous injections of AOM at 20 mg/kg body weight. At 12 weeks after the first injection, ten animals from each group were killed. The BR diet decreased colonic pH (P < 0·05) compared with the C diet. The total number of ACF observed decreased considerably in the BR/AOM group compared with the C/AOM group (P < 0·05). Comparison of similarity coefficients showed variability of colonic microbiota species between the different groups. In addition, we showed inter-individual variability within the same group. This similarity was affected by BR and AOM. The present results show that bifidobacteria numbers were lower in rats fed the BR diet compared with those fed the C diet. However, the number of enterobacteria in colonic content was increased (P < 0·05) in the BR group compared with the C group. The results from the present study show that the DF of BR reduced the incidence of AOM-induced ACF and increased microbiota biodiversity.

Red meat consumption is associated with increased risk of colorectal cancer. We have previously shown that haemin, Hb and red meat promote carcinogen-induced preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF) in rats. We have also shown that dietary Ca, antioxidant mix and olive oil inhibit haemin-induced ACF promotion, and normalize faecal lipoperoxides and cytotoxicity. Here we tested if these strategies are effective also against red meat promotion in dimethylhydrazine-induced rats. Three diets with 60 % beef meat were supplemented with calcium phosphate (31 g/kg), antioxidant agents (rutin and butylated hydroxyanisole, 0·05 % each) and olive oil (5 %). ACF, MDF, faecal water cytotoxicity, thiobarbituric acid reactive substances (TBARS) and urinary 1,4-dihydroxynonane mercapturic acid (DHN-MA) were measured. Beef meat diet increased the number of ACF (+30 %) and MDF (+100 %) (P < 0·001), which confirms our previous findings. Promotion was associated with increased faecal water TBARs ( × 4) and cytotoxicity ( × 2), and urinary DHN-MA excretion ( × 15). Ca fully inhibited beef meat-induced ACF and MDF promotion, and normalized faecal TBARS and cytotoxicity, but did not reduce urinary DHN-MA. Unexpectedly, high-calcium control diet-fed rats had more MDF and ACF in the colon than low-Ca control diet-fed rats. Antioxidant mix and olive oil did not normalize beef meat promotion nor biochemical factors. The results confirm that haem causes promotion of colon carcinogenesis by red meat. They suggest that Ca can reduce colorectal cancer risk in meat-eaters. The results support the concept that toxicity associated with the excess of a useful nutrient may be prevented by another nutrient.

Diet-induced changes in the activities of bacterial enzymes are known to play a role in colon cancer development. Resveratrol has been implicated as a protective agent in carcinogenesis. In the present study, the effect of resveratrol on the activities of faecal and colonic biotransforming enzymes such as β-glucuronidase, β-glucosidase, β-galactosidase, mucinase, nitroreductase and faecal sulfatase activity was assessed. The total number of aberrant crypt foci and their distribution in the proximal, medial and distal colon were observed in 1,2-dimethylhydrazine (DMH)-induced rats (group 3) and other treatment groups (groups 4–6). DMH (0.02g/kg body weight) was given subcutaneously once a week for 15 consecutive weeks, and the experiment was terminated at 30 weeks. DMH-treated rats showed elevated levels of cancer-associated bacterial enzyme activities, whereas on resveratrol supplementation in three different regimens, rats showed lowered activities. Resveratrol supplementation throughout the experimental period (group 6) exerted a more pronounced effect (P<0·01) by modulating the development of aberrant crypt foci and the activities of bacterial enzymes than did the other treatment regimens (groups 4 and 5). Thus, the present results demonstrate the inhibitory effect of resveratrol on DMH-induced colon carcinogenesis in rats.