Arthrospira (Spirulina) platensis feeding reduces the early stage of chemically induced rat colon carcinogenesis.

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.

Dietary Capsaicin Reduces Chemically Induced Rat Urinary Bladder Carcinogenesis.

Capsaicin (CAP) is the compound responsible for pungency in chili peppers, presenting several biological properties. But its general safety and effectiveness in the context of carcinogenesis has not been fully clarified. Thus, the present study evaluated whether dietary CAP modifies the development of urothelial lesions induced by the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male Sprague-Dawley rats. Animals were randomly allocated into 6 groups: G1 - treated with 0.05% BBN in drinking water (weeks 1-12) and received a balanced diet (weeks 1-20); G2 and G3-treated with BBN (weeks 1-12) and received a balanced diet with 0.01 or 0.02% CAP (weeks 1-20), respectively; G4 and G5- only received a balanced diet with 0.01 or 0.02% CAP (weeks 1-20), respectively; G6 - only received a balanced diet (weeks 1-20). At the end of week 20, the incidence and types of urothelial lesions, proliferating cell nuclear antigen (PCNA) labeling index, and matrix metalloproteinases (MMP) 2 and 9 activities were analyzed. A significant reduction was observed in the incidence and multiplicity of simple (p = 0.020 and p = 0.011) and nodular/papillary (p = 0.030 and p = 0.003) hyperplasias and papillomas/carcinomas (p = 0.023 and p = 0.020), epithelial proliferation (p = 0.007) and in the activity of the intermediate form of MMP-2 (p < 0.001) and pro-MMP-9 activities (p < 0.002), in BBN + 0.02% CAP (G3) group in comparison to BBN (G1) group. Capsaicin intake per se did not alter body weight, liver and kidney weights, urothelial histology or serum biochemical parameters. Thus, dietary CAP was safe and showed a protective effect against rat BBN-induced urothelial carcinogenesis.

Capsaicin lacks tumor-promoting effects during colon carcinogenesis in a rat model induced by 1,2-dimethylhydrazine.

Capsaicin (CPS, 8-methyl-N-vanillyl-trans-6-nonenamide), a pungent alkaloid from chili peppers, has contradictory effects in both experimental and human carcinogenesis. Thus, we evaluated the modifying effects of chronic CPS during the promotion and progression stages of rat colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Male Wistar rats were given four subcutaneous injections of DMH (40 mg/body weight (b.w.)) twice a week, for 2 weeks. After DMH-induced tumor initiation, the animals were treated with CPS at 5 or 50 mg/kg b.w. by gavage for 24 weeks (three times a week). High-dose CPS reduced both cell proliferation in adjacent "normal-appearing" colonic crypts and the total number of preneoplastic aberrant crypt foci (ACF) but did not change the number of dysplastic ACF or ACF multiplicity. Although the proportion of adenomas was increased, and tubular adenocarcinomas decreased in high-dose CPS, both CPS interventions exerted no effects on total tumor incidence, volume, multiplicity, cell proliferation (Ki-67), and apoptosis (caspase-3). In accordance, high-dose CPS treatment had discrete effects on gene expression in colon tumors, as only 3/94 (3.19%) genes were significantly modified (downregulation of Cebpd and Fasl, and upregulation of Jag1). The findings of the present study show that CPS does not impact on the promotion/progression stages of rat colon carcinogenesis. Therefore, CPS at a high-dose intervention showed to be a safe food ingredient.

Capsaicin reduces genotoxicity, colonic cell proliferation and preneoplastic lesions induced by 1,2-dimethylhydrazine in rats.

Capsaicin (8-Methyl-N-vanillyl-(trans)-6-nonenamide) is the major pungent ingredient found in chili peppers consumed worldwide. Most reports on capsaicin potential carcinogenicity have yielded inconsistent findings. Some studies have shown that capsaicin exerts anti-proliferative and pro-apoptotic effects on different cancer cell lines, while others have reported an association between capsaicin at high doses with mutagenicity and carcinogenicity. Thus, this study aimed at assessing the effects of capsaicin administration on 1,2-dimethyl-hydrazine (DMH)-induced colon carcinogenesis in male Wistar rats. Our results show that capsaicin administration, before and during carcinogen exposure, modified DMH-induced cytotoxicity and genotoxicity, promoting anti-proliferative and pro-apoptotic responses through the expression of the genes involved in apoptosis, cell cycle suppression and cell/tissue differentiation. Furthermore, capsaicin reduced aberrant crypt foci (ACF) number and multiplicity, although there were no differences in tumor incidence and multiplicity among the groups. Taken together, the results suggest that capsaicin may have a preventive effect against DMH-induced colorectal carcinogenesis.

Yacon (Smallanthus sonchifolius) and Lactobacillus acidophilus CRL 1014 reduce the early phases of colon carcinogenesis in male Wistar rats.

The modifying effects of aqueous yacon extract (AYE) and Lactobacillus acidophilus CRL 1014 against colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in male Wistar rats were investigated. Animals were allocated into five groups: G1: untreated group; G2: DMH-treated group; G3: DMH+L. acidophilus-treated group; G4: DMH+AYE-treated group; G5: DMH+L. acidophilus and AYE-treated group. A significant reduction (p<0.05) in leukocyte DNA damage and in colonic cell proliferation was observed after the first DMH administration in G3 (probiotic), G4 (prebiotic) and G5 (synbiotic) groups. In this moment, a significant increase (p<0.05) in colonic apoptosis was also observed in G3 (probiotic) and G5 (synbiotic) groups. In special, at five months after DMH administrations, a significant reduction (p<0.05) in ACF development was observed in G3 (probiotic), G4 (prebiotic) and G5 (synbiotic) groups. Incidence of colon tumors was lower at five months in G4 (prebiotic) and G5 (synbiotic) groups but not in eight months after DMH administrations. In conclusion, the findings suggest that the oral treatments have potential effects as a chemopreventive agent against colon carcinogenesis on an early stage of tumor development.

Potential effects of the herbicide Diuron on mammary and urinary bladder two-stage carcinogenesis in a female Swiss mouse model.

The potential promoting effect of Diuron was investigated in a mouse model of mammary and urinary bladder carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Four-week old female Swiss mice were allocated to five groups: Groups G1-G3 received DMBA (5 x 1.5 mg/mouse) and BBN (8 x 7.5 mg/mouse) and G4 and G5 groups received only vehicles during the first 6 weeks. At week 7, G1 and G5 groups received basal diet and G2, G3 and G4 groups were fed a diet containing Diuron at 1,250, 2,500 and 2,500 ppm, respectively, during 13 weeks. At week 20, the animals were euthanized and the gross tumors were registered. Mammary glands and urinary bladder were processed for histopathological analysis. Samples from non-tumor areas were evaluated for cell proliferation by 5-bromodeoxyuridine labeling index (BrdU-LI%) and apoptosis. Dietary treatment with Diuron at 1,250 and 2,500 ppm significantly increased BrdU-LI% (P < 0.05) and the incidence of simple/nodular urothelial hyperplasia in the urinary bladder from DMBA/BBN-initiated groups (G2 and G3 vs. G1, P < 0.02) and in the non-initiated group (G4 vs. G5, P = 0.042). Two transitional cell carcinomas were observed in the group initiated and fed Diuron 2,500 ppm (G3). In contrast, in the mammary gland, Diuron feeding for 13 weeks did not significantly alter cell proliferation and apoptosis indexes or the incidence of hyperplastic lesions or neoplasms in the DMBA/BBN-initiated groups. These findings suggest that Diuron is a promoting agent to the urinary bladder but not to the mammary gland in female Swiss mice submitted to a medium-term two-stage carcinogenesis bioassay.