Differential Induction of NAD(P)H:Quinone Oxidoreductase by Anti-Carcinogenic Organosulfides from Garlic

• Published in: Biochemical and biophysical research communications Vol. 244; no. 3; pp. 917 - 920
• Main Authors: Singh, Shivendra V., Pan, Su Shu, Srivastava, Sanjay K., Xia, Hong, Hu, Xun, Zaren, Howard A., Orchard, John L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.03.1998
• Subjects: AGENTES ANTINEOPLASTICOS; AIL; AJO; ALLIUM SATIVUM; Allyl Compounds - pharmacology; Animals; Anticarcinogenic Agents - pharmacology; ANTINEOPLASTIC AGENTS; Benzo(a)pyrene - pharmacology; Carcinogens - pharmacology; Disulfides - pharmacology; Enzyme Induction - drug effects; Female; GARLIC; Garlic - chemistry; Lung - enzymology; MEDICAMENT CYTOSTATIQUE; Mice; NAD(P)H Dehydrogenase (Quinone) - biosynthesis; Plants, Medicinal; Propane - analogs & derivatives; Propane - pharmacology; Stomach - enzymology; Structure-Activity Relationship; Sulfides - pharmacology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1998.8352

This study was undertaken to elucidate the mechanism of organ specificity and differential efficacy of garlic organosulfides (OSCs) [diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS)] in preventing benzo(a)pyrene (BP)-induced tumorigenesis in mice. The results of the present study reveal a good correlation between chemopreventive efficacies of garlic OSCs and their inductive effects on the expression of NAD(P)H:quinone oxidoreductase (NQO), an enzyme implicated in the detoxification of activated quinone metabolites of BP. Treatment of mice with DADS and DATS, which are potent inhibitors of BP-induced forestomach tumorigenesis, resulted in a statistically significant increase (2.4- and 1.5-fold, respectively) in forestomach NQO activity. In addition, DADS and DATS were much more potent inducers of forestomach NQO activity than DAS, which is a weak inhibitor of BP-induced forestomach tumorigenesis than the former compounds. Propyl-group containing OSCs (DPS and DPDS), which do not inhibit BP-induced tumorigenesis, did not affect forestomach NQO activity. Similar to forestomach, a good correlation was also observed between effects of these OSCs against BP-induced pulmonary tumorigenesis and their effects on NQO expression in the lung. For example, treatment of mice with DAS, which is a potent inhibitor of BP-induced pulmonary tumorigenesis, resulted in about 3.2-fold increase in pulmonary NQO activity. On the other hand, this activity was increased by about 1.5-fold upon DATS administration, which does not inhibit BP-induced cancer of the lung. In conclusion, our results suggest that induction of NQO may be important in anti-cancer effects of garlic OSCs.