Induction of Apoptosis by Diallyl Sulfide in DMBA-Induced Mouse Skin Tumors

Abstract

Diallyl sulfide (DAS), an organosulfur compound in garlic, has received increasing attention as a potential cancer-chemopreventive agent. DAS has been shown to possess antitumorigenic potential in various rodent tumor models. The present study demonstrates induction of apoptosis as the possible mechanism of the antiproliferative effect of DAS in solid tumors, as evident by the appearance of a sub-G₁ fraction in flow cytometry. Biochemical analysis of skin tumors revealed other characteristic features of apoptosis, including formation of DNA ladders on agarose gel, compaction of nuclear DNA, and formation of apoptotic bodies. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay of skin tumorsof DAS-supplemented animals showed a significant increase in the number of apoptotic cells compared with animals exposed to 7,12-dimethylbenz[a]anthracene alone. The increase in apoptotic index in nonmalignant and malignant tumors was 78% and 94%, respectively, in DAS-pretreated animals and 68% and 82%, respectively, in animals given DAS 1 h after carcinogen administration. These observations suggest that induction of apoptosis may be the major contributing factor for antitumorigenic properties of DAS.