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Colorectal cancer chemoprevention by 2 beta-cyclodextrin inclusion compounds of auraptene and 4'-geranyloxyferulic acid.

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.
AuthorsTakuji Tanaka, Mariangela B M de Azevedo, Nelson Durán, Joel B Alderete, Francesco Epifano, Salvatore Genovese, Mayu Tanaka, Takahiro Tanaka, Massimo Curini
JournalInternational journal of cancer (Int J Cancer) Vol. 126 Issue 4 Pg. 830-40 (Feb 15 2010) ISSN: 1097-0215 [Electronic] United States
PMID19688830 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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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