title: A bitter diterpenoid furanolactone columbin from Calumbae Radix inhibits azoxymethane-induced rat colon carcinogenesis.
abstract: The modifying effect of dietary administration of a diterpenoid furanolactone columbin isolated from the crude drug Calumbae Radix (the root of Jateorhiza columba MIERS, Menispermacea) on azoxymethane (AOM)-induced was investigated in male F344 rats. Animals were initiated with AOM (three weekly subcutaneous injections of 15 mg/kg body weight) to induce colonic neoplasms. They were fed the experimental diets mixed with columbin (4, 20, and 100 ppm) for 4 weeks, starting 1 week before the first dosing of AOM and thereafter maintained on the basal diet without columbin. Additional experimental groups included the AOM alone group, the columbin alone group (100 ppm in diet for 4 weeks), and the untreated control group. Dietary feeding of columbin (4, 20, and 100 ppm) during the initiation phase of AOM-induced colon carcinogenesis reduced the incidence and multiplicity of colonic adenocarcinoma and the inhibition by feeding of 20 ppm (incidence: 20%, P=0.0242 and multiplicity: 0.20+/-0.40, P<0.02) and 100 ppm (incidence: 10%, P=0.0029 and multiplicity: 0.10+/-0.30, P<0.002) columbin was significant when compared with the AOM alone group (incidence: 55% and multiplicity: 0.55+/-0.50). Also, columbin administration in diet lowered the number of argyrophilic nucleolar organizer regions protein per nucleus in non-lesional colonic crypts and the blood polyamine content, which are reflected in cell proliferation activity. These results indicate chemopreventive ability of dietary columbin against chemically induced colon tumorigenesis when fed during the initiation phase, providing a scientific basis for chemopreventive ability of columbin against human colon cancer.
authors.affiliation: Department of Pathology, Kanazawa Medical University, Uchinada, 920-0293, Ishikawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kohno
authors.forename: Masayo
authors.initials: M
authors.lastname: Maeda
authors.forename: Mikio
authors.initials: M
authors.lastname: Tanino
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tsukio
authors.forename: Naomi
authors.initials: N
authors.lastname: Ueda
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Sugie
authors.forename: Hideki
authors.initials: H
authors.lastname: Mori
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001397:Azoxymethane; D002273:Carcinogens; D002467:Cell Nucleus / Q000378:metabolism; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000188:drug therapy*; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D009092:Mucous Membrane / Q000473:pathology; D009929:Organ Size; D011073:Polyamines / Q000097:blood; D051381:Rats; D011916:Rats, Inbred F344; D013729:Terpenes / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D004224:Diterpenes; D007783:Lactones; D011073:Polyamines; D013729:Terpenes; C062514:columbin; D001397:Azoxymethane