(8-Hydroxyquinoline) Gallium(III) Complex with High Antineoplastic Efficacy for Treating Colon Cancer via Multiple Mechanisms

Abstract

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 (IC50 = 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.

First Gallium and Indium Crystal Structures of Curcuminoid Homoleptic Complexes: All-Different Ligand Stereochemistry and Cytotoxic Potential

“…Notably (DiMeOC) 2 -Ga exhibited up to three times lower toxicity than cisplatin. These findings suggest that (DiMeOC) 2 -Ga is a promising therapeutic agent, with gallium seeming to provide greater potency and selectivity in the cancer lines; this has been confirmed in studies of gallium metallodrugs as promising treatments for various types of cancer [48,49]. In fact, the curcumin-gallium and diacetylcurcumin-gallium complexes have been reported to have promising antioxidant and cytotoxic activities on prostate, breast, and bladder cancer cell lines [50,51].…”

Gallium complex K6 inhibits colorectal cancer by increasing ROS levels to induce DNA damage and enhance phosphatase and tensin homolog activity

“…synthesized a series of (8‐hydroxyquinoline) Ga(III) complexes and found that they have antitumor activity in A549 and HCT116 cells. 33 , 34 In this study, we screened several gallium complexes and found that K6, which also contains ligand 8‐hydroxyquinoline, has the strongest anticancer activity against CRC in vitro and in vivo. Importantly, K6 could induce DNA damage and activate the mitochondrial‐dependent apoptosis pathway.…”