The Osteosarcoma Stem Cell Activity of a Gallium(III)‐Phenanthroline Complex Appended to Salicylate

We report the synthesis, characterisation, and anti‐osteosarcoma properties of a gallium(III) complex (1) comprising of two 1,10‐phenanthroline ligands and salicylate, a non‐steroidal anti‐inflammatory drug. The gallium(III) complex 1 displays micromolar potency towards bulk osteosarcoma cells and osteosarcoma stem cells (OSCs). Notably, the gallium(III) complex 1 exhibits significantly higher toxicity towards OSCs grown in monolayer and three‐dimensional cultures than cisplatin, a frontline anti‐osteosarcoma drug. Nuclei isolation and immunoblotting studies show that the gallium(III) complex 1 enters osteosarcoma cell nuclei and induces DNA damage. Flow cytometry and cytotoxicity studies (in the presence of prostaglandin E2) indicate that the gallium(III) complex 1 downregulates cyclooxygenase‐2 (COX‐2) expression and kills osteosarcoma cells in a COX‐2‐dependent manner. Further, the mode of osteosarcoma cell death evoked by the gallium(III) complex 1 is characterised as caspase‐dependent apoptosis.