(8-Hydroxyquinoline) Gallium(III) Complex with High Antineoplastic Efficacy for Treating Colon Cancer Via Multiple Mechanisms
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A series of (8-hydroxyquinoline) gallium(III) complexes (CP--) 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- exhibited excellent cytotoxicity against HCT116 cancer cells (IC = 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- affected the expression of DNA-related proteins, which led to the apoptosis of cancer cells. Moreover, molecular docking tests of CP- were performed to predict other binding sites and to confirm its higher binding force to disulfide isomerase (PDI) proteins. The emissive properties of CP- suggest that this complex can be used for colon cancer diagnosis and treatment, as well as imaging. These results also provide a foundation for the development of gallium complexes as potent anticancer agents.
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