A bitter diterpenoid furanolactone columbin from Calumbae Radix inhibits azoxymethane-induced rat colon carcinogenesis.
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.
Kohno
Hiroyuki
H
Department of Pathology, Kanazawa Medical University, Uchinada, 920-0293, Ishikawa, Japan.
Maeda
Masayo
M
Tanino
Mikio
M
Tsukio
Yoshiaki
Y
Ueda
Naomi
N
Wada
Keiji
K
Sugie
Shigeyuki
S
Mori
Hideki
H
Tanaka
Takuji
T
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
D000970:Antineoplastic Agents; D002273:Carcinogens; D004224:Diterpenes; D007783:Lactones; D011073:Polyamines; D013729:Terpenes; C062514:columbin; D001397:Azoxymethane