82 resultados para colon motility
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The present study evaluated the chemopreventive potential of mate tea-like intake on mammary and colon carcinogenesis initiated by 7,12-dimethylbenz(a)antracene (DMBA) and 1,2-dimethylhydrazine (DMH) in female Swiss mice. After the initiation period, the animals received basal diet and organic mate tea-like, conventional mate tea-like, or green tea (positive control) at 2.0% as the drinking fluid during 15 weeks. At week 20, colon and mammary gland were analyzed for preneoplastic and neoplastic lesions development. Colon and mammary gland complexes were processed for cell proliferation analysis, estimated by proliferating cell nuclear antigen labeling index (PCNA-LI%). Specially, organic mate tea-like reduced the values of PCNA-LI% in colonic crypts (p < .003) and in mammary glands (p < .05) in DMBA/DMH-initiated groups. A lower incidence of aberrant crypt foci (ACF) in colon (p = .03) and of hyperplastic and neoplastic lesions in mammary gland (p < .05 and p < .02, respectively) was observed in DMBA/DMH-initiated groups treated with organic mate tea-like. These results suggest that post-initiation treatment with organic mate tea-like inhibited the development of colon and mammary carcinogenesis in a two-step medium-term mouse carcinogenesis model.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Colorectal cancer (CRC) is a disease whose genesis may include metabolic dysregulation. Cancer stem cells are attractive targets for therapeutic interventions since their aberrant expansion may underlie tumor initiation, progression, and recurrence. To investigate the actions of metabolic regulators on cancer stem cell-like cells (CSC) in CRC, we determined the effects of soybean-derived bioactive molecules and the anti-diabetes drug metformin (MET), alone and together, on the growth, survival, and frequency of CSC in human HCT116 cells. Effects of MET (60 μM) and soybean components genistein (Gen, 2 μM), lunasin (Lun, 2 μM), β-conglycinin (β-con, 3 μM), and glycinin (Gly, 3 μM) on HCT116 cell proliferation, apoptosis, and mRNA/protein expression and on the frequency of the CSC CD133(+)CD44(+) subpopulation by colonosphere assay and fluorescence-activated cell sorting/flow cytometry were evaluated. MET, Gen, and Lun, individually and together, inhibited HCT116 viability and colonosphere formation and, conversely, enhanced HCT116 apoptosis. Reductions in frequency of the CSC CD133(+)CD44(+) subpopulation with MET, Gen, and Lun were found to be associated with increased PTEN and reduced FASN expression. In cells under a hyperinsulinemic state mimicking metabolic dysregulation and without and with added PTEN-specific inhibitor SF1670, colonosphere formation and frequency of the CD133(+)CD44(+) subpopulation were decreased by MET, Lun and Gen, alone and when combined. Moreover, MET + Lun + Gen co-treatment increased the pro-apoptotic and CD133(+)CD44(+)-inhibitory efficacy of 5-fluorouracil under hyperinsulinemic conditions. Results identify molecular networks shared by MET and bioavailable soy food components, which potentially may be harnessed to increase drug efficacy in diabetic and non-diabetic patients with CRC.
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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.
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Pós-graduação em Medicina Veterinária - FCAV
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)