TANAKA, TAKUJIAZEVEDO, MARIANGELA B.M.DURAN, NELSONALDERETE, JOEL B.EPIFANO, FRANCESCOGENOVESE, SALVATORETANAKA, MAYUTANAKA, TAKAHIROCURINI, MASSIMO2014-07-312014-07-312014-07-312014-07-312010TANAKA, TAKUJI; AZEVEDO, MARIANGELA B.M.; DURAN, NELSON; ALDERETE, JOEL B.; EPIFANO, FRANCESCO; GENOVESE, SALVATORE; TANAKA, MAYU; TANAKA, TAKAHIRO; CURINI, MASSIMO. Colorectal cancer chemoprevention by 2 'Beta'-cyclodextrin inclusion compounds of auraptene and 4'-geranyloxyferulic acid. <b>International Journal of Cancer</b>, v. 126, n. 4, p. 830-840, 2010. DOI: <a href="https://dx.doi.org/10.1002/ijc.24833">10.1002/ijc.24833</a>. Disponível em: http://repositorio.ipen.br/handle/123456789/8051.0020-7136http://repositorio.ipen.br/handle/123456789/8051The inhibitory effects of novel prodrugs, inclusion complexes of 3-(40 -geranyloxy-30 -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/b-CD or AUR/b-CD for 15 weeks. At Week 18, the development of colonic adenocarcinoma was significantly inhibited by feeding with GOFA/b-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 6 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/b-CD and AUR/b-CD inhibited colonic inflammation and also modulated proliferation, apoptosis and the expression of several proinflammatory cytokines, such as nuclear factor-kappaB, tumor necrosis factor-a, Stat3, NF-E2-related factor 2, interleukin (IL)-6 and IL-1b, which were induced in the adenocarcinomas. Our findings indicate that GOFA/b-CD and AUR/b-CD, especially GOFA/b-CD, are therefore able to inhibit colitis-related colon carcinogenesis by modulating inflammation, proliferation and the expression of proinflammatory cytokines in mice.830-840closedAccessneoplasmslarge intestineinhibitiondrugschemotherapypreventive medicineArtigo de periódico412610.1002/ijc.24833