Abstract : Sulforaphane (SFR) an isothiocyanate from cruciferous vegetables possesses growth-inhibiting and ap
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Abstract : Sulforaphane (SFR) an isothiocyanate from cruciferous vegetables possesses growth-inhibiting and apoptosis-inducing activities in cancer cell lines. Recently SFR has been shown to promote the mitochondrial formation of reactive oxygen species (ROS) in human cancer cell lines. The present study was undertaken to see whether SFR-derived ROS might cause DNA damage in cultured human cells namely T limphoblastoid Jurkat and human umbilical vein endothelial cells (HUVEC). 1-3 h treatments with 10-30 microM SFR elicited intracellular ROS formation (as assayed with dihydrorhodamine DHR oxidation) as well as DNA breakage (as assessed with fast halo assay FHA). These effects lacked cell-type specificity since could be observed in both Jurkat and HUVEC. Differential-pH FHA analysis of damaged DNA showed that SFR causes frank DNA single strand breaks (SSBs) no DNA double strand breaks (DSBs) were found within the considered treatment times (up to 3 h). SFR-derived ROS were formed at the mitochondrial respiratory chain (MRC) level indeed rotenone or myxothiazol (MRC Complex I and III inhibitors respectively) abrogated ROS formation. Furthermore ROS were not formed in Jurkat cells pharmacologically depleted of respiring mitochondria (MRC-/Jurkat). Formation of ROS was causally linked to the induction of SSBs indeed all the experimental conditions capable of preventing ROS formation also prevented the damage of nuclear DNA from SFR-intoxicated cells. As to the toxicological relevance of SSBs we found that their prevention slightly but significantly attenuated SFR cytotoxicity suggesting that high-dose SFR toxicity is the result of a complex series of events among which GSH depletion seems to play a pivotal role. In conclusion the present study identifies a novel mechanism contributing to SFR toxicity which - since DNA damage is a prominent mechanism underlying the cytotoxic activity of established antineoplastic agents - might help to exploit the therapeutic value of SFR in anticancer drug protocols.Copyright 2010 Elsevier B.V. All rights reserved.PMID 20510253 PubMed - indexed for MEDLINEPublication Types MeSH Terms SubstancesPublication Types Research Support Non-U.S. GovtMeSH TermsAnticarcinogenic Agents/toxicity*Cell LineCell Survival/drug effectsCells CulturedDNA Breaks Single-StrandedHumansJurkat CellsMitochondria/metabolism*Reactive Oxygen Species/metabolism*Thiocyanates/toxicity*SubstancesAnticarcinogenic AgentsReactive Oxygen SpeciesThiocyanatessulforafanLinkOut - more resourcesFull Text SourcesElsevier ScienceEBSCOOhioLINK Electronic Journal CenterSwets Information Services Supplemental Content Related citations Sulforaphane generates reactive oxygen species leading to mitochondrial perturbation for apoptosis in human leukemia U937 cells. Biomed Pharmacother. 2008 Sulforaphane generates reactive oxygen species leading to mitochondrial perturbation for apoptosis in human leukemia U937 cells.Choi WY Choi BT Lee WH Choi YH. Biomed Pharmacother. 2008 Nov 62(9)637-44. Epub 2008 Feb 11. 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Compound (MeSH Keyword) PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles. Substance (MeSH Keyword) PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles. Recent activity Clear Turn Off Turn On Sulforaphane induces DNA single strand breaks in cultured human cells. Sulforaphane induces DNA single strand breaks in cultured human cells.Mutat Res. 2010 Jul 7 689(1-2)65-73. Epub 2010 May 25 . PubMed Your browsing activity is empty. Activity recording is turned off. Turn recording back on See more... 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