Zheng Li-Fang, Dai Fang, Zhou Bo, Yang Li, Liu Zhong-Li
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China.
Food Chem Toxicol. 2008 Jan;46(1):149-56. doi: 10.1016/j.fct.2007.07.010. Epub 2007 Jul 26.
The prooxidant effect of hydroxycinnamic acids (HCAs), i.e., caffeic acid (CaA), chlorogenic acid (ChA), sinapic acid (SA), ferulic acid (FA), 3-hydroxycinnamic acid (3-HCA) and 4-hydroxycinnamic acid (4-HCA) on supercoiled pBR322 plasmid DNA strand breakage and calf thymus DNA damage in the presence of Cu(II) ions has been studied. It was found that the compounds bearing ortho-dihydroxyl group (CaA and ChA) or bearing 4-hydroxy-3-methoxyl group (SA and FA) exhibited remarkably higher activity in the DNA damage than the ones bearing no such functionalities. The good correlation between the DNA damaging activity and the oxidative potential of the compounds indicates that the electron transfer between HCAs and Cu(II) plays a crucial role in the reaction. UV-Visible spectral changes demonstrated that CaA or ChA can chelate with Cu(II) as a bidentate ligand, hence facilitating intramolecular electron transfer between CaA or ChA and Cu(II). The involvement of reactive oxygen species (ROS) and Cu(I) ions in the DNA damage were affirmed by the inhibition of DNA breakage using mannitol, glutathione (GSH), catalase and bathocuproinedisulfonic acid (BCDS). These results may have important implications regarding the proposed mechanism of apoptosis induced by phenol and endogenous metal ions.
研究了羟基肉桂酸（HCAs），即咖啡酸（CaA）、绿原酸（ChA）、芥子酸（SA）、阿魏酸（FA）、3-羟基肉桂酸（3-HCA）和4-羟基肉桂酸（4-HCA）在Cu（II）离子存在下对超螺旋pBR322质粒DNA链断裂和小牛胸腺DNA损伤的促氧化作用。发现带有邻二羟基（CaA和ChA）或带有4-羟基-3-甲氧基（SA和FA）的化合物在DNA损伤方面表现出比不具有此类官能团的化合物显著更高的活性。化合物的DNA损伤活性与氧化电位之间的良好相关性表明，HCAs与Cu（II）之间的电子转移在反应中起关键作用。紫外可见光谱变化表明，CaA或ChA可以作为双齿配体与Cu（II）螯合，从而促进CaA或ChA与Cu（II）之间的分子内电子转移。使用甘露醇、谷胱甘肽（GSH）、过氧化氢酶和 bathocuproinedisulfonic acid（BCDS）对DNA断裂的抑制作用证实了活性氧（ROS）和Cu（I）离子参与了DNA损伤。这些结果可能对酚类和内源性金属离子诱导细胞凋亡的拟议机制具有重要意义。
