Abstract |
The inhibitory effects of novel prodrugs, inclusion complexes of 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans propenoic acid (GOFA) and auraptene (AUR) with beta-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/beta-CD or AUR/beta-CD for 15 weeks. At Week 18, the development of colonic adenocarcinoma was significantly inhibited by feeding with GOFA/beta-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/beta-CD suppressed the development of colonic adenocarcinomas. The dietary administration with GOFA/beta-CD and AUR/beta-CD inhibited colonic inflammation and also modulated proliferation, apoptosis and the expression of several proinflammatory cytokines, such as nuclear factor-kappaB, tumor necrosis factor-alpha, Stat3, NF-E2-related factor 2, interleukin (IL)-6 and IL-1beta, which were induced in the adenocarcinomas. Our findings indicate that GOFA/beta-CD and AUR/beta-CD, especially GOFA/beta-CD, are therefore able to inhibit colitis-related colon carcinogenesis by modulating inflammation, proliferation and the expression of proinflammatory cytokines in mice.
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Authors | Takuji Tanaka, Mariangela B M de Azevedo, Nelson Durán, Joel B Alderete, Francesco Epifano, Salvatore Genovese, Mayu Tanaka, Takahiro Tanaka, Massimo Curini |
Journal | International journal of cancer
(Int J Cancer)
Vol. 126
Issue 4
Pg. 830-40
(Feb 15 2010)
ISSN: 1097-0215 [Electronic] United States |
PMID | 19688830
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans-propenoic acid
- Birc5 protein, mouse
- Coumarins
- Diterpenes
- Inhibitor of Apoptosis Proteins
- Interleukin-1beta
- Interleukin-6
- Microtubule-Associated Proteins
- NF-kappa B
- Proliferating Cell Nuclear Antigen
- Propionates
- Repressor Proteins
- Survivin
- Tumor Necrosis Factor-alpha
- beta-Cyclodextrins
- aurapten
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Topics |
- Animals
- Colonic Neoplasms
(drug therapy, pathology)
- Colorectal Neoplasms
(drug therapy, epidemiology, mortality, prevention & control)
- Coumarins
(therapeutic use)
- Diterpenes
(therapeutic use)
- Humans
- Immunohistochemistry
- Incidence
- Inflammation
(drug therapy, etiology, pathology)
- Inflammatory Bowel Diseases
(complications)
- Inhibitor of Apoptosis Proteins
- Interleukin-1beta
(metabolism)
- Interleukin-6
(metabolism)
- Male
- Mice
- Mice, Inbred ICR
- Microtubule-Associated Proteins
(metabolism)
- NF-kappa B
(metabolism)
- Proliferating Cell Nuclear Antigen
(metabolism)
- Propionates
(therapeutic use)
- Repressor Proteins
- Survivin
- Tumor Necrosis Factor-alpha
(metabolism)
- beta-Cyclodextrins
(therapeutic use)
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