Organometallic Gold(III) Complexes Similar to Tetrahydroisoquinoline Induce ER-Stress-Mediated Apoptosis and Pro-Death Autophagy in A549 Cancer Cells
Organometallic Gold(III) Complexes Similar to Tetrahydroisoquinoline Induce ER-Stress-Mediated Apoptosis and Pro-Death Autophagy in A549 Cancer Cells
复制标题
类似于四氢异喹啉的有机金属金 (III) 络合物可诱导 A549 癌细胞中内质网应激介导的细胞凋亡和促死亡自噬
DOI：
10.1021/acs.jmedchem.7b01694
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发表时间：
2018-04-26
影响因子：
7.3
通讯作者：
Liang, Hong
中科院分区：
文献类型：
--
作者：
Huang, Ke-Bin;Wang, Feng-Yang;Liang, Hong
Agents inducing both apoptosis and autophagic death can be effective chemotherapeutic drugs. In our present work, we synthesized two organometallic gold(III) complexes harboring CAN ligands that structurally resemble tetrahydroisoquinoline (THIQ): Cyc-Au-1 ((AuLCl2)-Cl-1, L-1 = 3,4-dimethoxyphenethylamine) and Cyc-Au-2 ((AuLCl2)-Cl-2, L-2 = methylenedioxyphenethylamine). In screening their in vitro activity, we found both gold complexes exhibited lower lower resistance factors, and better anticancer activity toxicity, than those of cisplatin. The organometallic gold(III) complexes accumulate in mitochondria and induce elevated ROS and an ER stress response through mitochondrial dysfunction. These effects ultimately result in simultaneous apoptosis and autophagy. Importantly, compared to cisplatin, Cyc-Au-2 exhibits lower toxicity and better anticancer activity in a murine tumor model. To the best of our knowledge, Cyc-Au-2 is the first organometallic Au(III) compound that induces apoptosis and autophagic death. On the basis of our results, we believe Cyc-Au-2 to be a promising anticancer agent or lead compound for further anticancer drug development.
