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首页> 外文期刊>Journal of Molecular Biology >Tumor cell growth inhibition and extracellular signal-regulated kinase (ERK) phosphorylation by novel K vitamins.
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Tumor cell growth inhibition and extracellular signal-regulated kinase (ERK) phosphorylation by novel K vitamins.

机译：新型K维生素抑制肿瘤细胞生长和细胞外信号调节激酶（ERK）磷酸化。

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摘要

2-(2-hydroxy-ethylsulfanyl)-3-methyl-1,4-naphthoquinone or CPD-5, a K vitamin analog, was previously indicated to be a potent growth inhibitor for Hep 3B hepatoma cells in vitro. Here, we show that CPD-5 and two newly synthesized analogs, 2-(2-hydroxy-ethylsulfanyl)-3-methyl-5- nitro-1,4-naphthoquinone (PD-37) and 2-(2-hydroxy-ethylsulfanyl)-3- methyl-5-acetylamino-1,4-naphthoquinone (PD-42), are potent growth inhibitors of 13 different human cancer cell lines, with IC50 values in the range of 3-54 microM. Phospho-ERK was induced by each of three K vitamin analogs in every cell line in a dose-dependent manner, at growth inhibitory doses. ERK phosphorylation and growth inhibitory effects were strongly correlated, with p=0.0080 for CPD-5, p=0.0076 for PD-37 and p=0.0251 for PD-42. The induction of phospho-ERK and growth inhibition were antagonized by thiol-containing anti-oxidants, but not by catalase, consistent with a possible arylating mechanism. The data show a novel class of growth inhibitors with a wide spectrum of action that induces ERK hyper-phosphorylation, as a possible new growth inhibitory feature. Copyright 2001 Academic Press.
机译：先前已指出，2-（2-羟基-乙基硫烷基）-3-甲基-1,4-萘醌或CPD-5（一种K维生素类似物）是体外Hep 3B肝癌细胞的有效生长抑制剂。在这里，我们显示CPD-5和两个新合成的类似物2-（2-羟基-乙基硫烷基）-3-甲基-5-硝基-1,4-萘醌（PD-37）和2-（2-羟基- （乙硫基）-3-甲基-5-乙酰氨基-1,4-萘醌（PD-42）是13种不同人类癌细胞系的有效生长抑制剂，IC50值在3-54 microM范围内。在每个细胞系中，三种K维生素类似物均以生长抑制剂量以剂量依赖的方式诱导磷酸化ERK。 ERK磷酸化和生长抑制作用密切相关，CPD-5的p = 0.0080，PD-37的p = 0.0076，PD-42的p = 0.0251。磷酸-ERK的诱导和生长抑制被含硫醇的抗氧化剂拮抗，但过氧化氢酶则没有，这与可能的芳基化机理一致。数据表明，一类新型的生长抑制剂具有广泛的作用，可诱导ERK超磷酸化，这可能是一种新的生长抑制特征。版权所有2001学术出版社。

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