In vitro and in vivo studies of a decanuclear Ni(II) complex as a potential anti-breast cancer agent

A non-platinum-metal decanuclear complex [Ni 10 L 4 (CH 3 COO) 8 (C 2 H 5 OH) 8 ]·8(C 2 H 5 OH) ( Ni 10 complex) has been developed with a tri-dentate 2,3-dihydroxybenzaldehyde-2-aminophenol Schiff base ligand (H 3 L). Single crystal X-ray analysis reveals that the Ni 10 complex displays a sandwich loaf-shaped decanuclear structure and its anticancer activity was evaluated. The cell cytotoxicity results indicating that the Ni 10 complex is most effective to human breast cancer cells MDA-MB-231 and its mechanism were further investigated. Flow cytometry analysis showed that the Ni 10 complex triggered cell cycle arrest and induced apoptosis of MDA-MB-231 cells. Western blot analysis of the changes of intracellular protein expression showed that Ni 10 triggers MDA-MB-231 apoptosis through mitochondrial mediated apoptosis signaling pathways. In vivo experiments showed that the Ni 10 complex significantly suppressed breast tumor growth with low toxicity against major organs in a nude mice model. The good treatment effect, low toxicity and pharmacological mechanisms of the decanuclear Ni II complex may provide a clue for the research and development of non-platinum multinuclear based chemotherapeutic drugs.