RESUMO
PURPOSE: The aim of this study was to assess the effects of resistance and aerobic exercise on colorectal cancer (CRC) development in mice induced by azoxymethane (AOM) coupled with colitis. METHODS: Forty animals induced with CRC were used, divided into five groups of eight animals each: sedentary; continuous aerobics; continuous anaerobic; aerobic PI; and anaerobic PI. AOM was administered to the animals in two doses of 10 mg/kg each over the course of two weeks, the first dose administered in the third week and the second administered in the fourth. For the colitis, three cycles of dextran sodium sulfate were administered for five days, separated by two weeks of water. The 14th week of the experiment saw the euthanasia, the removal of their colons, and the creation of microscopy slides for histological analysis. RESULTS: Preneoplastic lesions developed in all five groups; there were no significant differences between them. However, in terms of inflammatory symptoms, mucosal ulceration was much more frequently in the exercise groups than in the sedentary group (p = 0.016). The number of polyps overall (p = 0.002), the distal region's polyp development (p = 0.003), and the proximal region's polyp development (p = 0.04) were all statistically different than sedentary group. CONCLUSIONS: The study discovered no significant difference in disease activity index scores between groups, but there was a significant difference in the number of polyps and the presence of mucosal ulceration in the colon.
Assuntos
Colite , Neoplasias Colorretais , Treinamento Resistido , Humanos , Animais , Camundongos , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Colite/induzido quimicamente , Colite/patologia , Azoximetano/efeitos adversos , Camundongos Endogâmicos C57BL , Sulfato de Dextrana/efeitos adversosRESUMO
Inflammation is currently considered a hallmark of cancer and plays a decisive role in different stages of tumorigenesis, including initiation, promotion, progression, metastasis and resistance to antitumor therapies. Colorectal cancer is a disease widely associated with local chronic inflammation. Additionally, extrinsic factors such as infection may beneficially or detrimentally alter cancer progression. Several reports have noted the ability of various parasitic infections to modulate cancer development, favoring tumor progression in many cases and inhibiting tumorigenesis in others. The aim of our study was to determine the effects of excreted/secreted products of the helminth Taenia crassiceps (TcES) as a treatment in a murine model of colitis-associated colon cancer (CAC). Here, we found that after inducing CAC, treatment with TcES was able to reduce inflammatory cytokines such as IL-1ß, TNF-α, IL-33 and IL-17 and significantly attenuate colon tumorigenesis. This effect was associated with the inhibition of signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) phosphorylation. Furthermore, we determined that TcES interfered with LPS-induced NF-κB p65 activation in human colonic epithelial cell lines in a Raf-1 proto-oncogene-dependent manner. Moreover, in three-dimensional cultures, TcES promoted reorganization of the actin cytoskeleton, altering cell morphology and forming colonospheres, features associated with a low grade of aggressiveness. Our study demonstrates a remarkable effect of helminth-derived molecules on suppressing ongoing colorectal cancer by downregulating proinflammatory and protumorigenic signaling pathways.
Assuntos
Anti-Inflamatórios/administração & dosagem , Azoximetano/efeitos adversos , Colite/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Proteínas de Helminto/administração & dosagem , Taenia/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colite/induzido quimicamente , Colite/complicações , Neoplasias do Colo/etiologia , Modelos Animais de Doenças , Feminino , Proteínas de Helminto/farmacologia , Humanos , Interleucina-1beta/metabolismo , Interleucina-33/metabolismo , Camundongos , NF-kappa B/metabolismo , Fosforilação , Proto-Oncogene Mas , Fator de Transcrição STAT3/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Aberrant crypt foci (ACF) is the precursor lesion of colorectal carcinogenesis (CRC), one of the most common malignancies in the world. Many studies have reported that people with higher phytochemical intake are at a reduced risk of developing ACF. One example of the botanical potential of preventive plant products is Cnidoscolus aconitifolius (CA), commonly known as Chaya. This study evaluated the phenolic profile of CA and the effects of the daily consumption of CA leaf infusion on the formation of ACF, histopathological lesions, and molecular biomarkers after azoxymethane (AOM) and dextran sulfate sodium (DSS) induced premalignant colon lesions in rats treated with for 16 and 32 weeks. The phenolic composition of the CA infusion was identified by reversed phase-high performance liquid chromatography-diode array detection (RP-HPCC-DAD). After sacrifice, a 4 cm segment was collected from the distal part of the colon and stained with methylene blue to look for ACF. Furthermore, 4 µm of colon, liver, and kidney was collected and stained with hematoxylin and eosin for histopathological analysis, along with 7 µm of colon for immunohistochemistry analysis. Eleven phenolic compounds were identified in the infusions, and ACF formation was reduced by 29.5% at the subchronic and by 64.6% at chronic stages. Lesions on kidney, liver, and colon tissue were also reduced. Our data suggest that CA treatment has preventive effects against AOM-/DSS-induced premalignant colon lesions in colon rats at the promotion level, inhibiting the cell proliferation of early neoplastic lesions and colonic inflammation through the decrease of ß-catenin by 41.8% at the subchronic stage and 29% at the chronic stage, along with a 46.2% reduction of cyclooxygenase 2 (COX-2) at long term, despite a high expression of NF-κB (30.3% at the subchronic stage and 22.8% at the chronic stage).
Assuntos
Focos de Criptas Aberrantes/prevenção & controle , Euphorbiaceae/química , Extratos Vegetais/administração & dosagem , Substâncias Protetoras/administração & dosagem , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/patologia , Animais , Azoximetano/efeitos adversos , Colo/efeitos dos fármacos , Colo/patologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Humanos , Masculino , Extratos Vegetais/química , Folhas de Planta/química , Substâncias Protetoras/química , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: To investigate the expression of superoxide dismutase (SOD), with use of antioxidant inositol hexaphosfate, in the presence of the carcinogen azoxymethane, in FCA of colon rats. METHODS: Wistar rats (n=48) were distributed in four groups of 12 mice. Divided in control (n=12); with azoxymethane administration AOM (n=12); administration of IP6 (n=12) and with administration of IP6/AOM (n=12). The subcutaneous administration of azoxymethane happened in the week 3 and 4 of the experiment, in dose 20mg/Kg, weekly; and administration of IP6 to 1 percent in water of drinking for 6 weeks in the group 3 and 4. The identification of the expression SOD-1 was accomplished through the quantification imunohistochemistry by the image processing attended by computer in crypts and focus of aberrant crypts in right colon. RESULTS: The group control presented expression of SOD1, on average 16,0 percent; group AOM, 26,7 percent; group IP6, 16,9 percent; group IP6/AOM, 20,9 percent. Variance analysis among the groups, was calculated 0,0078. CONCLUSION: The azoxymethane increase expression SOD1, while inositol hexaphosphate decreases in a significant way the expression of SOD1 promoted by the administration of the carcinogen azoxymethane.(AU)
OBJETIVO: Investigar a expressão de superóxido dismutase, com uso de antioxidante inositol hexafosfato, na presença do carcinógeno azoximetano em FCA de cólon de ratos. MÉTODOS: Quarenta e oito ratos Wistar, distribuídos em 4 grupos, divididos em controle (n=12); com administração de azoximetano AOM (n=12); administração de IP6 (n=12) e com administração de IP6/AOM (n=12). A administração subcutânea de azoximetano aconteceu na semana 3 e 4 do experimento, em dose 20mg/Kg, semanal; e administração de IP6 a 1 por cento em água de beber durante 6 semanas no grupo 3 e 4. A identificação da expressão SOD1 foi realizada através da quantificação imunohistoquimíca pelo processamento de imagem assistida por computador em criptas e focos de cripta aberrante em cólon direito. RESULTADOS: O grupo controle apresentou expressão de SOD1, em média 16,0 por cento; grupo AOM, 26,7 por cento; grupo IP6, 16,9 por cento; grupo IP6/AOM, 20,9 por cento. Análise de variância entre os grupos calculou-se 0,0078. CONCLUSÃO: A expressão de SOD-1 mostrou aumento significativo na presença de azoximetano e quando administrou-se IP6 concomitante houve diminuição na expressão de SOD1 promovido pela administração do carcinógeno azoximetano.(AU)
Assuntos
Animais , Azoximetano/administração & dosagem , Azoximetano/efeitos adversos , Inositol/administração & dosagem , Inositol/efeitos adversos , Colo/patologia , Ratos WistarRESUMO
The role of dietary fiber in colon cancer is still not clear. Epidemiological studies suggest a protective role for high fiber intake. However the data suggest that the effects of fiber must be considered in the context of the total diet and its interactions with other dietary components. The typical Sonora diet is high in dietary fiber (7.8%) and the majority of this fiber (71%) is insoluble. Comparing the incidence of colon cancer in Sonora with its neighboring state of Arizona, in 1991, Sonora reported 40 cases of colon cancer, a population of 1,823,606, compared to 1432 for Arizona (3,763,322 inhabitants). The typical regional diet was evaluated for its protective effect in the development of colon cancer in rats injected with azoxymethane, AOM. The regional diet showed a tendency to protect against colon cancer, an incidence of 45% compared to 66% for the control diet, although this effect was not significant (p = 0.15). Further studies are needed to fully evaluate the diet and certain interactive dietary factors such as fat, quantity as well as type, protein, calcium and antioxidant nutrients.