Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells

卷:35

Wang, Yichong ; Dacosta, Christopher ; Wang, Wei ; Zhou, Zhigang ; Liu, Ming ; Bao, Yongping

关键词: Cruciferous vegetable;    Sulforaphane;    Selenium;    Thioredoxin reductase;    Nrf2;    Colon cancer;   

DOI  :  10.1016/j.nutres.2015.05.011

学科分类：食品科学和技术

【 摘 要 】

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. (C) 2015 Elsevier Inc. All rights reserved.