Chemoprevention of azoxymethane-induced rat aberrant crypt foci by dietary zerumbone isolated from Zingiber zerumbet.
The modifying effects of dietary feeding of zerumbone isolated from Zingiber zerumbet on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. Expression of cyclooxygenase (COX)-2 in colonic mucosa exposed to AOM and/or zerumbone was also assayed. In addition, we assessed the effects of zerumbone on cell proliferation activity of crypts by counting silver-stained nucleolar organizer regions protein (AgNORs) in colonic cryptal cell nuclei. To induce ACF rats were given three weekly subcutaneous injections of AOM (15 mg/kg body weight). They were also fed the experimental diet containing 0.01% or 0.05% zerumbone for 5 weeks, starting one week before the first dosing of AOM. AOM exposure produced 84+/-13 ACF/rat at the end of the study (week 5). Dietary administration of zerumbone caused reduction in the frequency of ACF: 72+/-17 (14% reduction) at a dose of 0.01% and 45+/-18 (46% reduction, p<0.001) at a dose of 0.05%. Feeding of zerumbone significantly reduced expression of COX-2 and prostaglandins in colonic mucosa. Zerumbone feeding significantly lowered the number of AgNORs in colonic crypt cell nuclei. These findings might suggest possible chemopreventive ability of zerumbone, through suppression of COX-2 expression, cell proliferating activity of colonic mucosa, and induction of phase II detoxification enzymes in the development of carcinogen-induced ACF.
Tanaka
T
T
Department of Pathology, Kanazawa Medical University, Ishikawa, Japan. takutt@kanazawa-med.ac.jp
Shimizu
M
M
Kohno
H
H
Yoshitani
S
S
Tsukio
Y
Y
Murakami
A
A
Safitri
R
R
Takahashi
D
D
Yamamoto
K
K
Koshimizu
K
K
Ohigashi
H
H
Mori
H
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D001397:Azoxymethane; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D004032:Diet; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009697:Nucleolus Organizer Region / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015230:Prostaglandin D2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000627:therapeutic use*; D016622:Silver Staining; D030521:Zingiberaceae
D016588:Anticarcinogenic Agents; D007527:Isoenzymes; D012717:Sesquiterpenes; C403304:zerumbone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase; D015232:Dinoprostone; D001397:Azoxymethane; D015230:Prostaglandin D2