State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China.
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China.
Food Chem. 2018 Jun 1;250:213-220. doi: 10.1016/j.foodchem.2018.01.069. Epub 2018 Jan 9.
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.
本研究旨在以儿茶酚型二苯乙烯（3,4-DHS）为模型分子，探讨具有儿茶酚骨架的膳食多酚为何倾向于表现出抗癌化学预防活性。只有儿茶酚型二苯乙烯（3,4-DHS）和外源 Cu(II) 的短期协同作用，表现出对 HepG2 细胞相对于正常 L02 细胞更强的选择性杀伤能力。机制研究表明，该 3,4-DHS/Cu(II) 体系可通过两个连续的质子丢失电子转移产生细胞外活性氧（ROS）和邻醌，随后 ROS 扩散到细胞内，导致更高的细胞内 ROS 积累，优先破坏氧化还原平衡，并更有效地诱导 HepG2 细胞发生线粒体依赖性细胞凋亡和坏死，而 L-02 细胞则不然。这项工作进一步证明，膳食儿茶酚型分子通过其依赖铜的促氧化剂作用表现出化学预防活性。
