Novel anti-carcinogenic activity of an organosulfide from garlic: inhibition of H-RAS oncogene transformed tumor growth in vivo by diallyl disulfide is associated with inhibition of p21H-ras processing.
In this study, we report a novel anticarcinogenic activity of an organosulfur compound from garlic, diallyl disulfide (DADS). DADS treatment significantly inhibited the growth of H-ras oncogene transformed tumors in nude mice. As compared to controls, the appearance of tumors was also delayed markedly by oral administration of DADS. The inhibition of tumor growth by DADS treatment correlated with the inhibition of p21H-ras membrane association in the tumor tissue. The levels of membrane associated p21H-ras were markedly lower in the tumor tissues of DADS treated mice as compared to controls. An opposite trend, however, was evident for cytosolic p21H-ras. Furthermore, DADS treatment resulted in a significant inhibition of hepatic as well as tumoral 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. These results indicate that DADS suppresses the growth of H-ras oncogene transformed tumors in nude mice by inhibiting the membrane association of tumoral p21H-ras.
Singh
S V
SV
Cancer Research Laboratory, Mercy Cancer Institute, Mercy Hospital of Pittsburgh, Pennsylvania 15219, USA.
Mohan
R R
RR
Agarwal
R
R
Benson
P J
PJ
Hu
X
X
Rudy
M A
MA
Xia
H
H
Katoh
A
A
Srivastava
S K
SK
Mukhtar
H
H
Gupta
V
V
Zaren
H A
HA
D000498:Allyl Compounds; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004220:Disulfides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005737:Garlic / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010946:Plants, Medicinal; D011499:Protein Processing, Post-Translational; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D004220:Disulfides; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C028009:diallyl disulfide; D016283:Proto-Oncogene Proteins p21(ras)