Impact of garlic organosulfides on p21(H-ras) processing.
This study describes the novel anticarcinogenic activity of diallyl disulfide, a naturally occurring organosulfide from garlic. Oral administration of diallyl disulfide resulted in a dose-dependent and significant inhibition of the growth of H-ras oncogene transformed NIH 3T3 cells implanted in nude mice. The effect of diallyl disulfide was apparent in terms of delay in the appearance of measurable tumors, tumor volume and tumor weight. On the other hand, the growth of H-ras oncogene transformed tumors was not inhibited by dipropyl disulfide, a naturally occurring saturated analog of diallyl disulfide. The diallyl disulfide-mediated inhibition of H-ras oncogene transformed tumor growth correlated with the inhibition of p21(H-ras) membrane association. The levels of membrane-associated p21(H-ras) were markedly lower in the tumors of diallyl disulfide-treated mice than in those of controls. An opposite trend, however, was evident for the cytosolic p21(H-ras). The results of this study indicate that diallyl disulfide inhibits the growth of H-ras oncogene transformed tumors in vivo by inhibiting the membrane association of p21(H-ras) and that the allyl group may be an important determinant in the inhibitory effect of this organosulfide on tumor growth.
Cancer Research Laboratory, Mercy Cancer Institute, The Mercy Hospital of Pittsburgh, Pittsburgh, PA 15219, USA.
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D016475:3T3 Cells; D000284:Administration, Oral; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000498:Allyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004220:Disulfides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051231:Farnesyltranstransferase; D005260:Female; D005737:Garlic / Q000378:metabolism*; D011905:Genes, ras / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010946:Plants, Medicinal; D011499:Protein Processing, Post-Translational; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D004220:Disulfides; D004791:Enzyme Inhibitors; C028009:diallyl disulfide; D006903:Hydroxymethylglutaryl CoA Reductases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D016283:Proto-Oncogene Proteins p21(ras)