title: Aged garlic extract inhibits 1,2-dimethylhydrazine-induced colon tumor development by suppressing cell proliferation.
abstract: Garlic and its constituents are reported to have a preventive effect against colorectal cancer in animal models. Aged garlic extract (AGE), which is produced by natural extraction from fresh garlic for more than 10 months in aqueous ethanol, also has reputed chemopreventive effects on colon carcinogenesis, but has never been studied for its effects on colon cancer development. We investigated the antitumor effects of AGE in rats with 1,2-dimethylhydrazine (DMH)-induced carcinogenesis, and the mechanism of AGE in human colon cancer cell proliferation. F344 rats randomly divided into three groups were administered DMH (20 mg/kg weight) subcutaneously once a week for 8 weeks in a basal diet. After the last injection, one group of rats was then moved onto a basal diet containing 3% wt/wt AGE, and rats were sacrificed at 8 or 31 weeks. The number of aberrant crypt foci (ACF), histological type of tumor and proliferative activity of the tumor lesions were analyzed by macroscopic, pathological and immunohistochemical methods. DLD-1 human colon cancer cells were utilized to investigate the effect of AGE on anti-cell proliferation. AGE decreased the number of ACF but had no effect on gross tumor pathology. AGE showed a lower number of adenoma and adenocarcinoma lesions by histological analysis. Immunohistochemical staining indicated that AGE suppressed the proliferative activity in adenoma and adenocarcinoma lesions, but showed no effect on normal colon mucosa. Moreover, we demonstrated that AGE delayed cell cycle progression by downregulating cyclin B1 and cdk1 expression via inactivation of NF-κB in the human colorectal cancer cells but did not induce apoptosis. These findings suggest that AGE has an antitumor effect through suppression of cell proliferation.
authors.affiliation: Program in Biological System Sciences, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Jikihara
authors.affiliation: Department of Health Science, Faculty of Human Culture Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.
authors.forename: Guangying
authors.initials: G
authors.lastname: Qi
authors.affiliation: Department of Health Science, Faculty of Human Culture Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Nozoe
authors.affiliation: Department of Health Science, Faculty of Human Culture Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Hirokawa
authors.affiliation: Department of Health Science, Faculty of Human Culture Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sato
authors.affiliation: Program in Biological System Sciences, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sugihara
authors.affiliation: Program in Biological System Sciences, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Shimamoto
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000230:Adenocarcinoma / Q000473:pathology; D000236:Adenoma / Q000473:pathology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology*; D005434:Flow Cytometry; D005737:Garlic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009374:Neoplasms, Experimental / Q000188:drug therapy; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D016588:Anticarcinogenic Agents; D002273:Carcinogens; D010936:Plant Extracts; D019813:1,2-Dimethylhydrazine