Differential induction of NAD(P)H:quinone oxidoreductase by anti-carcinogenic organosulfides from garlic.
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.
Singh
S V
SV
Cancer Research Laboratory, Mercy Hospital of Pittsburgh, Pennsylvania 15219, USA. ssingh@mercy.pmhs.org
Pan
S S
SS
Srivastava
S K
SK
Xia
H
H
Hu
X
X
Zaren
H A
HA
Orchard
J L
JL
D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D004220:Disulfides / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005737:Garlic / Q000737:chemistry*; D008168:Lung / Q000201:enzymology; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis*; D010946:Plants, Medicinal; D011407:Propane / Q000031:analogs & derivatives / Q000494:pharmacology; D013270:Stomach / Q000201:enzymology; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000494:pharmacology*
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004220:Disulfides; D013440:Sulfides; C042577:diallyl trisulfide; D001564:Benzo(a)pyrene; C028009:diallyl disulfide; C038491:allyl sulfide; D016660:NAD(P)H Dehydrogenase (Quinone); C041288:n-propyl disulfide; C087894:dipropyl sulfide; D011407:Propane