Differential induction of glutathione transferase isoenzymes of mice stomach by diallyl sulfide, a naturally occurring anticarcinogen.
Diallyl sulfide (DAS), an organosulfur compound identified as the flavor component in garlic, has been shown to inhibit chemically induced neoplasia of forestomach and lung in mice. Even though the exact mechanism(s) of anti-neoplastic activity of DAS is not known, several independent studies suggest that this effect may, at least in part, be due to the elevation of glutathione-S-transferase (GST) activity. To gain further insight into the mechanism(s) of anti-carcinogenic activity of DAS, we have determined effect of orally administered DAS (25, 50 and 75 mumol) on levels of alpha, mu and pi class GSTs and glutathione (GSH) peroxidase and GSH reductase activities of female A/J mice stomach. Western blotting revealed presence of alpha, mu and pi class GSTs in mice stomach. A significant increase in all the three classes of GSTs was observed in the stomach of mice treated with DAS. Maximum increase in GST alpha and pi was evident by treating the animals with 75 mumol DAS whereas maximum induction of GST mu occurred after treating mice with 50 mumol DAS. GSH peroxidase activity towards t-butyl-hydroperoxide increased in a dose-dependent fashion in the mice stomach treated with DAS. Even though this activity towards hydrogen peroxide was similar in mice treated with 50 or 75 mumol DAS, these values were significantly higher than that of the control. GSH reductase was also elevated in the stomach of mice treated with 75 mumol DAS. These results suggest that DAS may exert anti-neoplastic effect by modulating GSH dependent detoxification enzymes.
Maurya
A K
AK
Department of Oncology, University of Miami School of Medicine, Florida 33101.
Singh
S V
SV
D000498:Allyl Compounds; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D004790:Enzyme Induction / Q000187:drug effects; D004976:Ethacrynic Acid / Q000378:metabolism; D005737:Garlic; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D005980:Glutathione Reductase / Q000096:biosynthesis; D005982:Glutathione Transferase / Q000096:biosynthesis*; D007527:Isoenzymes / Q000096:biosynthesis*; D051379:Mice; D010946:Plants, Medicinal; D013270:Stomach / Q000187:drug effects* / Q000201:enzymology; D013440:Sulfides / Q000494:pharmacology*
D000498:Allyl Compounds; D000970:Antineoplastic Agents; D007527:Isoenzymes; D013440:Sulfides; C038491:allyl sulfide; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D004976:Ethacrynic Acid