Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice.
We previously reported the chemopreventive ability of a prenyloxycoumarin auraptene in chemically induced carcinogenesis in digestive tract, liver and urinary bladder of rodents. The current study was designed to determine whether dietary feeding of auraptene and its related prenyloxycoumarin collinin can inhibit colitis-related mouse colon carcinogenesis. The experimental diets, containing the compounds at 2 dose levels (0.01 and 0.05%), were fed for 17 weeks to male CD-1 (ICR) mice that were initiated with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and promoted by 1% (w/v) DSS in drinking water for 7 days. Their tumor inhibitory effects were assessed at week 20 by counting the incidence and multiplicity of colonic neoplasms and the immunohistochemical expression of proliferating cell nuclear antigen (PCNA)-labeling index, apoptotic index, cyclooxygenase (COX)-2, inducible nitric oxide (iNOS) and nitrotyrosine in colonic epithelial malignancy. Feeding with auraptene or collinin, at both doses, significantly inhibited the occurrence of colonic adenocarcinoma. In addition, feeding with auraptene or collinin significantly lowered the positive rates of PCNA, COX-2, iNOS and nitrotyrosine in adenocarcinomas, while the treatment increased the apoptotic index in colonic malignancies. Our findings may suggest that certain prenyloxycoumarins, such as auraptene and collinin, could serve as an effective agent against colitis-related colon cancer development in rodents.
Kohno
Hiroyuki
H
Department of Oncologic Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. h-kohno@kanazawa-med.ac.jp
Suzuki
Rikako
R
Curini
Massimo
M
Epifano
Francesco
F
Maltese
Federica
F
Gonzales
Sylvia Prieto
SP
Tanaka
Takuji
T
D000818:Animals; D000873:Anthracenes / Q000008:administration & dosage / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003092:Colitis / Q000150:complications*; D003110:Colonic Neoplasms / Q000209:etiology / Q000517:prevention & control*; D003374:Coumarins / Q000008:administration & dosage / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000187:drug effects; D004032:Diet; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects
C436726:5-hydroxy-6-methoxy-7-(3-methyl-but-2-enyloxy)-2H-1-benzopyran-2-one; D000873:Anthracenes; D016588:Anticarcinogenic Agents; D003374:Coumarins; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; C427741:collinone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C105832:aurapten