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Supplement: Recent Advances on the Nutritional Effects Associated with the Use of Garlic as a Supplement

Impact of Garlic Organosulfides on p21^H-ras Processing^{1 ,2}

Cancer Research Laboratory, Mercy Cancer Institute, The Mercy Hospital of Pittsburgh, Pittsburgh, PA 15219

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.

KEY WORDS: • garlic • organosulfides • diallyl disulfide • H-ras • growth inhibition

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