This study was aimed at understanding why dietary polyphenols with a catechol skeleton tend to exhibit cancer chemopreventive activity by using a catechol-type stilbene (3,4-DHS) as a model molecule. Only a short-term cooperation of 3,4-DHS and exogenous Cu(II) exhibited a strong preferential ability to kill HepG2 cells over normal L02 cells. Mechanism studies reveal that this 3,4-DHS/Cu(II) system could produce extracellularly reactive oxygen species (ROS) and o-quinone through two sequential proton loss electron transfer followed by diffusion of ROS into cells, leading to higher intracellular accumulation of ROS, preferential disruption of redox homeostasis and more effective mitochondria-dependent apoptosis as well as necrosis of HepG2 cells than L-02 cells. This work provides further evidence that dietary catechol-type molecules show chemopreventive activity by virtue of their copper-dependent prooxidant action.

这项研究旨在了解为什么具有邻苯二酚骨架的饮食多酚通过使用邻苯二酚型二苯乙烯（3,4-DHS）作为模型分子倾向于表现出化学预防癌症的活性。3,4-DHS和外源性Cu（II）的短期合作表现出比正常L02细胞更强的杀死HepG2细胞的优先能力。机理研究表明，该3,4-DHS / Cu（II）系统可产生细胞外活性氧（ROS）和邻苯二甲酸苯醌通过两个连续的质子损失电子转移，然后扩散到细胞中，导致ROS在细胞内的积累更高，氧化还原稳态的优先破坏和更有效的线粒体依赖性细胞凋亡以及HepG2细胞的坏死性高于L-02细胞。这项工作提供了进一步的证据，表明饮食中的儿茶酚类分子由于其铜依赖性的抗氧化剂作用而具有化学预防活性。