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Impact of garlic organosulfides on p21(H-ras) processing
1Cancer Research Laboratory, Mercy Cancer Institute, The Mercy Hospital of Pittsburgh, Pittsburgh, PA 15219, USA.
Abstract:
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.
Insights
Diallyl disulfide from garlic shows anticancer properties by inhibiting tumor growth in mice. This organosulfide works by preventing the H-ras oncogene protein from associating with cell membranes, suggesting the allyl group is key to its effect.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Garlic contains organosulfides with potential health benefits.
- The H-ras oncogene plays a role in cell transformation and tumor development.
- Diallyl disulfide (DADS) is a key organosulfide found in garlic.
Purpose of the Study:
- To investigate the anticarcinogenic activity of diallyl disulfide (DADS).
- To determine the effect of DADS on the growth of H-ras oncogene-transformed tumors in vivo.
- To elucidate the molecular mechanism underlying DADS's inhibitory effect on tumor growth.
Main Methods:
- Oral administration of DADS to nude mice bearing H-ras oncogene-transformed NIH 3T3 cell tumors.
- Monitoring tumor appearance, volume, and weight.
- Assessing the membrane and cytosolic association of p21(H-ras) protein in tumor tissues.
Main Results:
- DADS significantly inhibited tumor growth in a dose-dependent manner, delaying tumor appearance and reducing tumor volume and weight.
- Dipropyl disulfide, a saturated analog, did not inhibit tumor growth, highlighting the importance of the allyl group.
- DADS treatment led to decreased membrane-associated p21(H-ras) and increased cytosolic p21(H-ras) in tumors.
Conclusions:
- Diallyl disulfide exhibits novel anticarcinogenic activity against H-ras oncogene-transformed tumors in vivo.
- The mechanism involves the inhibition of p21(H-ras) membrane association.
- The allyl group of diallyl disulfide is crucial for its tumor-inhibitory effects.