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

被引：67

作者：

Eskandari, Arvin ^{[1
]}

Kundu, Arunangshu ^{[2
]}

Ghosh, Sushobhan ^{[2
]}

Suntharalingam, Kogularamanan ^{[3
]}

机构：

[1] Kings Coll London, Dept Chem, London SE1 1DB, England

[2] Gauhati Univ, Dept Chem, Gauhati 781014, Assam, India

[3] Univ Leicester, Dept Chem, Leicester LE1 7RH, Leics, England

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2019年 / 58卷 / 35期

关键词：

antitumor agents; cancer; DNA damage; multinuclear metal complexes; platinum; DNA; CISPLATIN; PHOSPHORYLATION; METALLOHELICES; RESISTANCE; DELIVERY; DRUGS; PHASE;

D O I：

10.1002/anie.201905389

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：12059 / 12064

页数：6

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