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 [Ni₁₀L₄(CH₃COO)₈ (C₂H₅OH)₈]·8(C₂H₅OH) (Ni₁₀ complex) has been developed with a tri-dentate 2,3-dihydroxybenzaldehyde-2-aminophenol Schiff base ligand (H₃L). Single crystal X-ray analysis reveals that the Ni₁₀ complex displays a sandwich loaf-shaped decanuclear structure and its anticancer activity was evaluated. The cell cytotoxicity results indicating that the Ni₁₀ complex is most effective to human breast cancer cells MDA-MB-231 and its mechanism were further investigated. Flow cytometry analysis showed that the Ni₁₀ 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 Ni₁₀ triggers MDA-MB-231 apoptosis through mitochondrial mediated apoptosis signaling pathways. In vivo experiments showed that the Ni₁₀ 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.