Induction of complementary function reductase enzymes in colon cancer cells by dithiole-3-thione versus sodium selenite.
Induction of complementary function reductase enzymes in colon cancer cells by dithiole-3-thione versus sodium selenite.
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二硫醇-3-硫酮与亚硒酸钠在结肠癌细胞中诱导互补功能还原酶。
DOI：
10.1002/jbt.21601
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发表时间：
2015
影响因子：
3.6
通讯作者：
Sturla,ShanaJ
中科院分区：
文献类型：
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作者：
Erzinger,MelanieM;Bovet,Cédric;Uzozie,Anuli;Sturla,ShanaJ
细胞对还原酶的诱导可以改变细胞对药物和化学物质的敏感性。在这项研究中，我们比较了单剂量亚硫酸钠和~3H-1，2-二硫醇-3-硫酮(D3T)随时间的变化对HT29细胞药物相关还原能力的影响，并在选择性反应监测质谱学的基础上定义了蛋白质对这一活性的特定贡献。硫氧还蛋白还原酶1(TrxR1)的蛋白水平和活性被硒诱导高达2.2倍。相反，硒对前列腺素还原酶1(PTGR1)和NAD(P)H：苯醌氧化还原酶1(NQO1)的活性和蛋白水平影响不大。强的Nrf2诱导剂D3T诱导了所有的还原酶，并增加了生物还原DNA烷基化药物羟甲基富烯的细胞毒性。这些数据和实验方法允许人们定义HT29细胞中还原酶PTGR1、TrxR1和NQO1的诱导效力，并将这些与药物细胞毒性的变化联系起来。
Cellular induction of reductase enzymes can alter the susceptibility of cells toward drugs and chemicals. In this study, we compared the capacity of a single dose of sodium selenite and 3H‐1,2‐dithiole‐3‐thione (D3T) to influence the drug‐relevant reducing capacity of HT29 cells over time, and defined the protein‐specific contribution to this activity on the basis of selected reaction monitoring mass spectrometry. Thioredoxin reductase 1 (TrxR1) protein levels and activity were inducible up to 2.2‐fold by selenium. In contrast, selenium had only a minor influence on prostaglandin reductase 1 (PTGR1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) activity and protein levels. D3T, a strong Nrf2 inducer, induced all the reductases and additionally increased the cytotoxicity of hydroxymethylacylfulvene, a bioreductive DNA‐alkylating drug. The data and experimental approaches allow one to define induction potency for reductase enzymes PTGR1, TrxR1, and NQO1 in HT29 cells and link these to changes in drug cytotoxicity.