Epidemiological and animal studies linking high and varied fruit and vegetable intake to lower cancer risk, suggest the theoretical possibility that regular, long-term mass administration of isolated naturally occurring dietary constituents can provide a means of controlling cancer incidence. Although no exact mechanism of molecular chemoprotection is known, it is believed that the up-regulation of phase-II metabolizing enzymes by phytoalexins, such as sulforaphane - released from its thioglucoside natural precursor, glucoraphanin, by myrosinase hydrolysis – an isothiocyanate found in Cruciferae, could provide a defence against carcinogens.With the aim to verify such hypothesis, the effects of glucoraphanin supplementation on xenobiotic metabolizing enzymes were thus investigated in male and female Sprague-Dawley rats (aged 6-7 weeks, 150±15 g) receiving per os daily either 24 or 48 mg/kg b.w. glucoraphanin and, for comparison, either 120 or 240 mg/kg b.w. of the palmizio cauliflower extract (PCE – OD74 containing the same amount of glucoraphanin) for four consecutive days; controls received saline only and liver microsomes tested for various CYPs.Glucoraphanin slightly affected phase-II “detoxifying” enzymes, but powerfully induced phase-I bioactivating enzymes (P<0.01, Wilcoxon) such as CYP1A1 (up to ~8.4-fold), CYP3A1/2 (~3-fold), CYP2C11 (~3-fold), CYP1A2 and CYP2B1 (~5.5-fold) and CYP2E1 (~2-fold) associated monooxygenases. Both induction (up to 1.5-fold, for CYP3A1/2) and inactivation (up to 86% loss for CYP2C11) were seen in PCE-OD74 supplemented rats. Results of the most affected isoforms (e.g. CYP3A1/2, CYP1A1/2 and CYP2E1) were sustained by means of Western immunoblotting. CYP induction was paralleled by a corresponding increase in mRNA.Electronic Paramagnetic Resonance (EPR) spectroscopy coupled to a spin-probe technique showed a link between CYP induction and free radical over-generation.
Anticancer enzyme-based dietary manipulating strategies: from the cruciferae extract to the isolated single constituent.
CANISTRO, DONATELLA;PEROCCO, PAOLO;BARILLARI, JESSICA;VALGIMIGLI, LUCA;PEDULLI, GIAN FRANCO;SAPONE, ANDREA;BROCCOLI, MASSIMILIANO;STRADIOTTI, ALESSANDRO;BIAGI, GIAN LUIGI;PAOLINI, MORENO
2005
Abstract
Epidemiological and animal studies linking high and varied fruit and vegetable intake to lower cancer risk, suggest the theoretical possibility that regular, long-term mass administration of isolated naturally occurring dietary constituents can provide a means of controlling cancer incidence. Although no exact mechanism of molecular chemoprotection is known, it is believed that the up-regulation of phase-II metabolizing enzymes by phytoalexins, such as sulforaphane - released from its thioglucoside natural precursor, glucoraphanin, by myrosinase hydrolysis – an isothiocyanate found in Cruciferae, could provide a defence against carcinogens.With the aim to verify such hypothesis, the effects of glucoraphanin supplementation on xenobiotic metabolizing enzymes were thus investigated in male and female Sprague-Dawley rats (aged 6-7 weeks, 150±15 g) receiving per os daily either 24 or 48 mg/kg b.w. glucoraphanin and, for comparison, either 120 or 240 mg/kg b.w. of the palmizio cauliflower extract (PCE – OD74 containing the same amount of glucoraphanin) for four consecutive days; controls received saline only and liver microsomes tested for various CYPs.Glucoraphanin slightly affected phase-II “detoxifying” enzymes, but powerfully induced phase-I bioactivating enzymes (P<0.01, Wilcoxon) such as CYP1A1 (up to ~8.4-fold), CYP3A1/2 (~3-fold), CYP2C11 (~3-fold), CYP1A2 and CYP2B1 (~5.5-fold) and CYP2E1 (~2-fold) associated monooxygenases. Both induction (up to 1.5-fold, for CYP3A1/2) and inactivation (up to 86% loss for CYP2C11) were seen in PCE-OD74 supplemented rats. Results of the most affected isoforms (e.g. CYP3A1/2, CYP1A1/2 and CYP2E1) were sustained by means of Western immunoblotting. CYP induction was paralleled by a corresponding increase in mRNA.Electronic Paramagnetic Resonance (EPR) spectroscopy coupled to a spin-probe technique showed a link between CYP induction and free radical over-generation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
