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Type: Artigo de periódico
Title: Colorectal Cancer Chemoprevention By 2 β-cyclodextrin Inclusion Compounds Of Auraptene And 4′-geranyloxyferulic Acid
Author: Tanaka T.
De Azevedo M.B.M.
Duran N.
Alderete J.B.
Epifano F.
Genovese S.
Tanaka M.
Tanaka T.
Curini M.
Abstract: The inhibitory effects of novel prodrugs, inclusion complexes of 3-(4′-geranyloxy-3′-methoxyphenyl)-2-trans propenoic acid (GOFA) and auraptene (AUR) with b-cyclodextrin (CD), on colon carcinogenesis were investigated using an azoxymethane (AOM)/ dextran sodium sulfate (DSS) model. Male CD-1 (ICR) mice initiated with a single intraperitoneal injection of AOM (10 mg/kg body weight) were promoted by the addition of 1.5% (w/v) DSS to their drinking water for 7 days. They were then given a basal diet containing 2 dose levels (100 and 500 ppm) of GOFA/β-CD or AUR/β-CD for 15 weeks. At Week 18, the development of colonic adenocarcinoma was significantly inhibited by feeding with GOFA/β-CD at dose levels of 100 ppm (63% reduction in multiplicity, p < 0.05) and 500 ppm (83% reduction in the multiplicity, p < 0.001), when compared with the AOM/DSS group (multiplicity: 3.36 ± 3.34). In addition, feeding with 100 and 500 ppm (p < 0.01) of AUR/b-CD suppressed the development of colonic adenocarcinomas. The dietary administration with GOFA/β-CD and AUR/β-CD inhibited colonic inflammation and also modulated proliferation, apoptosis and the expression of several proinflammatory cytokines, such as nuclear factor-kappaB, tumor necrosis factor-α, Stat3, NF-E2-related factor 2, interleukin (IL)-6 and IL-1β, which were induced in the adenocarcinomas. Our findings indicate that GOFA/β-CD and AUR/β-CD, especially GOFA/β-CD, are therefore able to inhibit colitis-related colon carcinogenesis by modulating inflammation, proliferation and the expression of proinflammatory cytokines in mice. © 2009 UICC.
Rights: fechado
Identifier DOI: 10.1002/ijc.24833
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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