Institut für Lebensmitteltechnologie und Lebensmittelchemie, Technische Universität Berlin, Berlin, Germany.
Arch Biochem Biophys. 2010 Apr 15;496(2):93-100. doi: 10.1016/j.abb.2010.02.002. Epub 2010 Feb 12.
Selected biological effects of 1,4-naphthoquinone, menadione (2-methyl-1,4-naphthoquinone) and structurally related quinones from natural sources--the 5-hydroxy-naphthoquinones juglone, plumbagin and the 2-hydroxy-naphthoquinones lawsone and lapachol--were studied in human keratinocytes (HaCaT). 1,4-naphthoquinone and menadione as well as juglone and plumbagin were highly cytotoxic, strongly induced reactive oxygen species (ROS) formation and depleted cellular glutathione. Moreover, they induced oxidative DNA base damage and accumulation of DNA strand breaks, as demonstrated in an alkaline DNA unwinding assay. Neither lawsone nor lapachol (up to 100 microM) were active in any of these assays. Cytotoxic and oxidative action was paralleled by stimulation of stress signaling: all tested quinones except lawsone and lapachol strongly induced phosphorylation of the epidermal growth factor receptor (EGFR) and the related ErbB2 receptor tyrosine kinase. EGFR activation by plumbagin, juglone and menadione was attenuated by a superoxide dismutase mimetic, indicating that ROS-related mechanisms contribute to EGFR activation by these naphthoquinones.
研究了 1,4-萘醌、甲萘醌（2-甲基-1,4-萘醌）以及天然来源的结构相关醌类物质（5-羟基萘醌胡桃醌、白花丹醌和 2-羟基萘醌 lawsone 和 lapachol）对人角质形成细胞（HaCaT）的某些生物学效应。1,4-萘醌、甲萘醌、胡桃醌和白花丹醌具有高度细胞毒性，可强烈诱导活性氧（ROS）的形成，并使细胞内谷胱甘肽耗竭。此外，正如在碱性 DNA 解旋试验中所证明的，它们还诱导氧化 DNA 碱基损伤和 DNA 链断裂的积累。lawsone 和 lapachol（最高达 100 μM）在任何这些试验中均无活性。细胞毒性和氧化作用与应激信号的刺激平行：除了 lawsone 和 lapachol 之外，所有测试的醌类物质都强烈诱导表皮生长因子受体（EGFR）和相关的 ErbB2 受体酪氨酸激酶的磷酸化。超氧化物歧化酶模拟物可减弱白花丹醌、胡桃醌和甲萘醌对 EGFR 的激活作用，表明这些萘醌类物质通过 ROS 相关机制激活 EGFR。
