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

doi:10.1006/bbrc.1998.8352

Biochemical and Biophysical Research Communications

Volume 244, Issue 3, 27 March 1998, Pages 917-920

https://doi.org/10.1006/bbrc.1998.8352 Get rights and content

Abstract

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.

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^☆: Anders, M. W.

¹: To whom correspondence should be addressed: Dr. Shivendra V. Singh, Cancer Research Laboratory, Mercy Hospital of Pittsburgh, 1400 Locust Street, Pittsburgh, PA 15219. Fax: (412) 232-5753. E-mail:[email protected].

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

Abstract

Chem.-Biol. Interact.

J. Biol. Chem.

Cancer Lett.

Arch. Biochem. Biophys.

Arch. Biochem. Biophys.

Methods Enzymol.

Anal. Biochem.

Carcinogenesis

Carcinogenesis

Cancer Res.

Physiol. Rev.

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