(8-Hydroxyquinoline) Gallium(III) Complex with High Antineoplastic Efficacy for Treating Colon Cancer via Multiple Mechanisms
Sihan Zhou, Wenhui Liao, Yun Yang, Wei Li, Yuanyuan Wu, Tiantian Wu, Shi‐Hui Deng, Jie Zhou, Zhe Li, Qi‐Hua Zhao, Jing‐Yuan Xu, Ceshi Chen, Ming‐Jin Xie
Abstract
High Resolution Image Download MS PowerPoint Slide A series of (8-hydroxyquinoline) gallium(III) complexes (CP- 1 – 4 ) was synthesized and characterized by single X-ray crystallography and density functional theory (DFT) calculation. The cytotoxicity of the four gallium complexes toward a human nonsmall cell lung cancer cell line (A549), human colon cancer cell line (HCT116), and human normal hepatocyte cell line (LO2) was evaluated using MTT assays. CP- 4 exhibited excellent cytotoxicity against HCT116 cancer cells (IC 50 = 1.2 ± 0.3 μM) and lower toxicity than cisplatin and oxaliplatin. We also evaluated the anticancer mechanism studies in cell uptake, reactive oxygen species analysis, cell cycle, wound-healing, and Western blotting assays. The results showed that CP- 4 affected the expression of DNA-related proteins, which led to the apoptosis of cancer cells. Moreover, molecular docking tests of CP- 4 were performed to predict other binding sites and to confirm its higher binding force to disulfide isomerase (PDI) proteins. The emissive properties of CP- 4 suggest that this complex can be used for colon cancer diagnosis and treatment, as well as in vivo imaging. These results also provide a foundation for the development of gallium complexes as potent anticancer agents.