title: The natural chemopreventive phytochemical R-sulforaphane is a far more potent inducer of the carcinogen-detoxifying enzyme systems in rat liver and lung than the S-isomer.
abstract: The chemopreventive activity of the phytochemical sulforaphane, (-)1-isothiocyanato-4R-(methylsulfinyl)-butane, present in cruciferous vegetables in substantial amounts in the form of glucosinolate, was demonstrated in animal models of cancer using the racemate, despite the fact that humans are exposed only to the R-enantiomer through the diet. Since a principal mechanism of the chemopreventive activity of sulforaphane is modulation of the carcinogen-metabolising enzyme systems, a study was conducted in precision-cut rat liver and lung slices, and in FAO cells comparing the ability of R- and S-sulforaphane to modulate these enzyme systems. R-sulforaphane elevated hepatic glutathione S-transferase and quinone reductase whereas the S-enantiomer had no effect; moreover, the R-enantiomer was more effective in up-regulating GSTα, GSTμ and quinone reductase protein levels. In the lung, both enantiomers increased the same enzyme activities with the R-enantiomer being more potent; in addition, the R-enantiomer was more effective in up-regulating GSTα and quinone reductase protein levels. Both isomers increased glutathione levels in both tissues, with R-sulforaphane being more potent. Finally, R-sulforaphane was the more effective of the two isomers in up-regulating CYP1A1/1B1 apoprotein levels in both liver and lung, and CYP1A2 in the liver. Similarly, in FAO cells the R-enantiomer was far more effective in up-regulating quinone reductase and glutathione S-transferase activities and protein levels compared with the S-isomer. These studies demonstrate clearly the superiority of R-sulforaphane, when compared with the S-enantiomer, in stimulating detoxification enzymes, and raises the possibility that the animal studies that employed the racemate may have underestimated the chemopreventive activity of this isothiocyanate.
authors: Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom.
authors: Ahmad Faizal
authors: AF
authors: Abdull Razis
authors: Renato
authors: R
authors: Iori
authors: Costas
authors: C
authors: Ioannides
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D004790:Enzyme Induction; D005982:Glutathione Transferase / Q000096:biosynthesis; D017879:Isothiocyanates; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D010944:Plants / Q000737:chemistry*; D051381:Rats; D013237:Stereoisomerism; D013454:Sulfoxides; D013861:Thiocyanates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase; C016766:sulforaphane