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Aged garlic extract inhibits 1,2-dimethylhydrazine-induced colon tumor development by suppressing cell proliferation.
Oncol Rep 2015; 33(3):1131-40OR

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+Show Affiliations

Program in Biological System Sciences, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.Department of Health Science, Faculty of Human Culture Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.Department of Health Science, Faculty of Human Culture Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.Department of Health Science, Faculty of Human Culture Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.Department of Health Science, Faculty of Human Culture Science, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.Program in Biological System Sciences, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.Program in Biological System Sciences, Prefectural University of Hiroshima, Minami-ku, Hiroshima 734-8558, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25573280

Citation

Jikihara, Hiroshi, et al. "Aged Garlic Extract Inhibits 1,2-dimethylhydrazine-induced Colon Tumor Development By Suppressing Cell Proliferation." Oncology Reports, vol. 33, no. 3, 2015, pp. 1131-40.
Jikihara H, Qi G, Nozoe K, et al. Aged garlic extract inhibits 1,2-dimethylhydrazine-induced colon tumor development by suppressing cell proliferation. Oncol Rep. 2015;33(3):1131-40.
Jikihara, H., Qi, G., Nozoe, K., Hirokawa, M., Sato, H., Sugihara, Y., & Shimamoto, F. (2015). Aged garlic extract inhibits 1,2-dimethylhydrazine-induced colon tumor development by suppressing cell proliferation. Oncology Reports, 33(3), pp. 1131-40. doi:10.3892/or.2014.3705.
Jikihara H, et al. Aged Garlic Extract Inhibits 1,2-dimethylhydrazine-induced Colon Tumor Development By Suppressing Cell Proliferation. Oncol Rep. 2015;33(3):1131-40. PubMed PMID: 25573280.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aged garlic extract inhibits 1,2-dimethylhydrazine-induced colon tumor development by suppressing cell proliferation. AU - Jikihara,Hiroshi, AU - Qi,Guangying, AU - Nozoe,Koichiro, AU - Hirokawa,Mayumi, AU - Sato,Hiromi, AU - Sugihara,Yuka, AU - Shimamoto,Fumio, Y1 - 2014/12/30/ PY - 2014/09/20/received PY - 2014/11/13/accepted PY - 2015/1/10/entrez PY - 2015/1/13/pubmed PY - 2015/11/4/medline SP - 1131 EP - 40 JF - Oncology reports JO - Oncol. Rep. VL - 33 IS - 3 N2 - 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. SN - 1791-2431 UR - https://www.unboundmedicine.com/medline/citation/25573280/Aged_garlic_extract_inhibits_12_dimethylhydrazine_induced_colon_tumor_development_by_suppressing_cell_proliferation_ L2 - http://www.spandidos-publications.com/or/33/3/1131 DB - PRIME DP - Unbound Medicine ER -