title: Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells.
abstract: Dietary isothiocyanates are potent inducers of the NF-E2-related factor 2 (Nrf2) pathway. Sulforaphane (SFN), a representative dietary isothiocyanate, has previously been shown to up-regulate antioxidant enzymes such as selenium (Se)-dependent thioredoxin reductase-1 (TrxR-1) in many tumor cell lines. In the present study, we hypothesized that a combination of SFN and Se would have a synergistic effect on the up-regulation of TrxR-1 and the protection against oxidative damage in the normal colonic cell line CCD841. Treatment of cells with SFN and Se significantly induced TrxR-1 expression. Pretreatment of cells with SFN protects against H2O2-induced cell death; this protection was enhanced by cotreatment with Se. The small interfering RNA knockdown of either TrxR-1 or Nrf2 reduced the protection afforded by SFN and Se cotreatment; TrxR-1 and Nrf2 knockdown reduced cell viabilities to 66.5% and 51.1%, respectively, down from 82.4% in transfection-negative controls. This suggests that both TrxR-1 and Nrf2 are important in SFN-mediated protection against free radical-induced cell death. Moreover, flow cytometric analysis showed that TrxR-1 and Nrf2 were involved in SFN-mediated protection against H2O2-induced apoptosis. In summary, SFN activates the Nrf2 signaling pathway and protects against H2O2-mediated oxidative damage in normal colonic cells. Combined SFN and Se treatment resulted in a synergistic up-regulation of TrxR-1 that in part contributed to the enhanced protection against free radical-mediated cell death provided by the cotreatment.
authors.affiliation: The 4(th) Affiliated Hospital, Harbin Medical University, Harbin 150081, P.R. China; Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK.
authors.forename: Yichong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dacosta
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: The 4(th) Affiliated Hospital, Harbin Medical University, Harbin 150081, P.R. China. Electronic address: mliu35@aliyun.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK. Electronic address: y.bao@uea.ac.uk.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Bao
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001937:Brassica / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism / Q000517:prevention & control; D004357:Drug Synergism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D034741:RNA, Small Interfering; D012643:Selenium / Q000494:pharmacology*; D015398:Signal Transduction; D013454:Sulfoxides; D054481:Thioredoxin Reductase 1 / Q000378:metabolism*; D014131:Trace Elements / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D034741:RNA, Small Interfering; D013454:Sulfoxides; D014131:Trace Elements; D006861:Hydrogen Peroxide; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; C016766:sulforaphane; D012643:Selenium
keywords: Colon cancer; Cruciferous vegetable; Nrf2; Selenium; Sulforaphane; Thioredoxin reductase