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Nitric Oxide-releasing Platinum(IV) Prodrug Efficiently Inhibits Proliferation and Metastasis of Cancer Cells

Abstract

Nitric oxide (NO) is a gaseous signaling molecule involved in many physiological and pathological processes. Here a NO-donor (furoxan derivative) has been conjugated to cisplatin, generating a dual-functional Pt(IV) prodrug Pt-furoxan. Upon cellular internalization, Pt-furoxan releases cytotoxic cisplatin and a signaling molecule NO that can modulate the cellular response to the platinum agent, leading to synergistic anti-proliferation effects. Interestingly, Pt-furoxan also demonstrates promising anti-metastasis effect both in vitro and in vivo. Mechanism investigations indicates that Pt-furoxan suppresses the activity of MMP9 and MMP2, two key enzymes involved in tumor metastasis, and effectively inhibits the adhesion of tumor cells to vascular endothelial cells. This result offers a novel strategy to construct dual-functional agents by conjugation of NO-donors for the prevention of both proliferation and metastasis of tumor cells.

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Supplementary files

Article information


Submitted
09 Aug 2020
Accepted
14 Oct 2020
First published
15 Oct 2020

Chem. Commun., 2020, Accepted Manuscript
Article type
Communication

Nitric Oxide-releasing Platinum(IV) Prodrug Efficiently Inhibits Proliferation and Metastasis of Cancer Cells

Y. Dai, Y. Zhu, J. Cheng, J. Shen, H. Huang, M. Liu, Z. Chen and Y. Liu, Chem. Commun., 2020, Accepted Manuscript , DOI: 10.1039/D0CC05422D

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