s-allylcysteine and Colonic-Neoplasms

Garlic has been reported to have chemopreventive effects against a variety of cancers. However, different garlic preparations contain different constituents. We investigated the chemopreventive effect of aged garlic extract (AGE), an odorless product from prolonged extraction of fresh garlic, on colon carcinogenesis and cell proliferation in 1,2-dimethylhydrazine (DMH)-induced colon neoplastic rats. Rats were given weekly subcutaneous injections of DMH (20 mg/kg) for 20 wk, and fed either a basal diet or one containing 4% AGE. Serum from AGE-treated rats contained detectable S-allylcysteine. The AGE diet significantly reduced the number of colon tumors and aberrant crypt foci compared to the basal diet. Cell proliferation of normal-appearing colonic mucosa was assessed by MIB-5 immunohistochemistry. AGE treatment significantly decreased the mean MIB-5-labeling index. These findings suggest AGE has a chemopreventive effect on colon carcinogenesis through suppression of cell proliferation.

Topics: 1,2-Dimethylhydrazine; Animals; Anticarcinogenic Agents; Carcinogens; Colonic Neoplasms; Cysteine; Disease Models, Animal; Garlic; Male; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley

Growth-inhibitory effects on DS19 mouse erythroleukemia cells were seen in the micromolar concentration range with allicin and S-allylmercaptocysteine and in the millimolar range with allyl butyrate, allyl phenyl sulfone, and S-allyl cysteine. Increased acetylation of histones was induced by incubation of cells with the allyl compounds at concentrations similar to those that resulted in the inhibition of cell proliferation. The induction of histone acetylation by S-allylmercaptocysteine was also observed in Caco-2 human colon cancer cells and T47D human breast cancer cells. In contrast to the effect on histone acetylation, there was a decrease in the incorporation of phosphate into histones when DS19 cells were incubated with 25 microM S-allylmercaptocysteine. Histone deacetylase activity was inhibited by allyl butyrate, but there was little or no effect with the allyl sulfur compounds examined in this study. A similar degree of downregulation of histone deacetylase and histone acetyltransferase was observed when DS19 cells were incubated with S-allylmercaptocysteine or allyl isothiocyanate. The induction of histone acetylation by S-allylmercaptocysteine was not blocked by a proteasome inhibitor. The mechanism by which S-allylmercaptocysteine induces histone acetylation remains to be characterized. It may be related in part to metabolism to allyl mercaptan, which is a more effective inhibitor of histone deacetylase.

Topics: Acetylation; Acetyltransferases; Allyl Compounds; Animals; Antineoplastic Agents; Breast Neoplasms; Colonic Neoplasms; Cysteine; Disulfides; Electrophoresis, Polyacrylamide Gel; Female; Histone Acetyltransferases; Histone Deacetylases; Histones; Humans; Leukemia, Erythroblastic, Acute; Leupeptins; Mice; Saccharomyces cerevisiae Proteins; Sulfinic Acids; Tumor Cells, Cultured

Organosulfur compounds (OSCs) present in garlic and onion oil have been shown to inhibit chemical carcinogenesis. In this study, we compared the chemopreventive efficacy of five lipid- and four water-soluble OSCs using the murine nuclear aberration assay. Administration of diallyl sulfide and S-allyl cysteine p.o. at a dose of 200 mg/kg 3 h prior to i.p. 1,2-dimethylhydrazine (DMH) injection (20 mg/kg) significantly inhibited colonic nuclear damage in female C57Bl/6J mice by 47% and 36%, respectively. The inhibitory effect of S-allyl cysteine was found to be dose dependent. The other OSCs did not affect the level of DMH-induced nuclear toxicity. Furthermore, the incidence and frequency of colonic tumors induced by DMH (20 mg/kg, 10 weekly i.p. injections) in female CF-1 mice were significantly inhibited by S-allyl cysteine pretreatment, given 3 h prior to each carcinogen injection. These data indicate that the allyl group coupled to a single sulfur atom might play an important structural role in inhibition of DMH-induced colonic nuclear toxicity and carcinogenesis. OSCs containing allyl groups stimulated glutathione S-transferase activity in both the liver and colon. However, their saturated analogues stimulated little or no hepatic and colonic glutathione S-transferase activity. Induction of hepatic and colonic glutathione S-transferase might assist in detoxification of carcinogens and could be necessary for some aspects of chemoprevention.

Topics: 1,2-Dimethylhydrazine; Animals; Antineoplastic Agents; Body Weight; Carcinogens; Colonic Neoplasms; Cysteine; Dimethylhydrazines; Disulfides; Female; Mice; Mice, Inbred C57BL; Structure-Activity Relationship; Sulfides