NOVEL ANTICARCINOGENIC ACTIVITY OF AN ORGANOSULFIDE FROM GARLIC - INHIBITION OF H-RAS ONCOGENE-TRANSFORMED TUMOR GROWTH IN-VIVO BY DIALLYL DISULFIDE IS ASSOCIATED WITH INHIBITION OF P21(H-RAS) PROCESSING

In this study, we report a novel anticarcinogenic activity of an organ osulfur compound fro garlic, diallyl disulfide (DADS). DADS treatment significantly inhibited the growth of H-ras oncogene transformed tumor s in nude mice. As compared to controls, the appearance of tumors was also delayed markedly by oral administration of DADS. The inhibition o f tumor growth by DADS treatment correlated with the inhibition of p21 (H-ras) membrane association in the tumor tissue. The levels of membra ne associated p21(H-ras) were markedly lower in the tumor tissues of D ADS treated mice as compared to controls. An opposite trend, however, was evident for cytosolic p21(H-ras). Furthermore, DADS treatment resu lted in a significant inhibition of hepatic as well as tumoral 3-hydro xy-3-methylglutaryl coenzyme A reductase activity. These results indic ate that DADS suppresses the growth of H-ras oncogene transformed tumo rs in nude mice by inhibiting the membrane association of tumoral p21( H-ras). (C) 1996 Academic Press, Inc.