A Triangular Platinum(II) Multinuclear Complex with Cytotoxicity Towards Breast Cancer Stem Cells

Abstract

The preparation of multinuclear metal complexes offers a route to novel anticancer agents and delivery systems. The potency of a novel triangular multinuclear complex containing three platinum atoms, Pt-3, towards breast cancer stem cells (CSCs) is reported. The trinuclear platinum(II) complex, Pt-3 exhibits selective toxicity towards breast CSCs over bulk breast cancer cells and non-tumorigenic breast cells. Remarkably, Pt-3 inhibits the formation, size, and viability of mammospheres to a better extent than salinomycin, an established CSC-potent agent, and cisplatin and carboplatin, clinically used platinum drugs. Mechanism of action studies show that Pt-3 effectively enters breast CSCs, penetrates the nucleus, induces genomic DNA damage, and prompts caspase-dependent apoptosis. To the best of our knowledge, Pt-3 is the first multinuclear platinum complex to selectively kill breast CSCs over other breast cell types.

Keywords: DNA damage; antitumor agents; cancer; multinuclear metal complexes; platinum.