A Triangular Platinum(II) Multi-nuclear Complex with Impressive Cytotoxicity Towards Breast Cancer Stem Cells.

Abstract

The preparation of multi-nuclear metal complexes offers a route to novel anticancer agents and delivery systems. The potency of a novel triangular multi-nuclear complex containing three platinum atoms, Pt-3, towards breast cancer stem cells (CSCs) is reported. The tri-nuclear platinum(II) complex, Pt-3 exhibits selectivity 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 multi-nuclear platinum complex to selectivity kill breast CSCs over other breast cell types