PMID- 25573280 OWN - NLM STAT- MEDLINE DCOM- 20151103 LR - 20240109 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 33 IP - 3 DP - 2015 Mar TI - Aged garlic extract inhibits 1,2-dimethylhydrazine-induced colon tumor development by suppressing cell proliferation. PG - 1131-40 LID - 10.3892/or.2014.3705 [doi] AB - 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-kappaB 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. FAU - Jikihara, Hiroshi AU - Jikihara H AD - Program in Biological System Sciences, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan. FAU - Qi, Guangying AU - Qi G AD - Department of Health Science, Faculty of Human Culture Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan. FAU - Nozoe, Koichiro AU - Nozoe K AD - Department of Health Science, Faculty of Human Culture Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan. FAU - Hirokawa, Mayumi AU - Hirokawa M AD - Department of Health Science, Faculty of Human Culture Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan. FAU - Sato, Hiromi AU - Sato H AD - Department of Health Science, Faculty of Human Culture Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan. FAU - Sugihara, Yuka AU - Sugihara Y AD - Program in Biological System Sciences, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan. FAU - Shimamoto, Fumio AU - Shimamoto F AD - Program in Biological System Sciences, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141230 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Anticarcinogenic Agents) RN - 0 (Carcinogens) RN - 0 (Plant Extracts) RN - IX068S9745 (1,2-Dimethylhydrazine) SB - IM MH - 1,2-Dimethylhydrazine/toxicity MH - Adenocarcinoma/pathology MH - Adenoma/pathology MH - Animals MH - Anticarcinogenic Agents/*pharmacology MH - Blotting, Western MH - Carcinogens/toxicity MH - Cell Line, Tumor MH - Cell Proliferation/*drug effects MH - Colonic Neoplasms/*pathology MH - Flow Cytometry MH - Garlic MH - Humans MH - Immunohistochemistry MH - Male MH - Neoplasms, Experimental/drug therapy MH - Phytotherapy/*methods MH - Plant Extracts/*pharmacology MH - Rats MH - Rats, Inbred F344 EDAT- 2015/01/13 06:00 MHDA- 2015/11/04 06:00 CRDT- 2015/01/10 06:00 PHST- 2014/09/20 00:00 [received] PHST- 2014/11/13 00:00 [accepted] PHST- 2015/01/10 06:00 [entrez] PHST- 2015/01/13 06:00 [pubmed] PHST- 2015/11/04 06:00 [medline] AID - 10.3892/or.2014.3705 [doi] PST - ppublish SO - Oncol Rep. 2015 Mar;33(3):1131-40. doi: 10.3892/or.2014.3705. Epub 2014 Dec 30.