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.