The chemopreventive properties of cruciferous vegetables: Is oxidative stress in cancer cell cytotoxicity induced by glucosinolate hydrolysis products?

Abstract

Abstracts / Toxicology 290 (2012) 103–148 119 and MCL5 (metabolically competent that express CYP1A1, 1A2,2E1, 2A6, 3A4 and epoxide hydrolase) cells were determinedafter the cells (2.0×10 5 ) were treated for 24h with theglucosinolate hydrolysis products; prop-2-enylisothiocyanate, 3-butenylnitrile, 3,4-epithiobutylnitrile, but-3-enylisothiocyanate,4,5-epithiopentylnitrile and pent-4-enylnitrile. The glucosinolatehydrolysis products were synthesized as previously described(Luethy et al., 1981). Oxidative stress was determined fluoromet-rically using carboxy-H2DCFDA as an indicator of reactive oxygenspecies(ROS),asdescribedbythemanufacturer(MolecularProbes,USA).A significant increase in oxidative stress for both prop-2-enylisothiocyanate (AITC) and 3,4 epithiobutylnitriles (3,4 ETN) inMCL-5cells(Fig.1B)wasnoted.NosignificantinductionofROSwasfound for 3-butenylnitrile (BN), but-3-enylisothiocyanate (BITC),4,5-epithiopentylnitrile (4,5 ETN) and pent-4-enylnitrile (PN). Incontrast,noneofthesixglucosinolatehydrolysisproductsinducedROS in the metabolically non-competent cHo1 cells, suggestingthat P450s mediated oxidation was involved in ROS productionby AITC and 3,4 ETN. The oxidative stress induced by prop-2-enylisothiocyanate has been associated with the electrophilicityof SH group due to a shorter methylene chain resulting in greatertoxicity(Murataetal.,2000).However,themechanismofROSpro-duction by 3,4 epithiobutylnitrile is not understood. Both AITC and3,4ETNarecytotoxicandtheirabilitytogenerateROSmediatedviacyp metabolism is likely to contribute to this toxicity. The lack ofROS induction by BN, BITC, 4,5 ETN and BN is consistent with theirlack of toxicity in these cell lines.References