The cytotoxic mechanisms of disulfiram and copper(II) in cancer cells

Patricia Erebi Tawari; Zhipeng Wang; Mohammad Najlah; Chi Wai Tsang; Vinodh Kannappan; Peng Liu; Christopher McConville; Bin He; Angel L. Armesilla; Weiguang Wang

doi:10.1039/C5TX00210A

The cytotoxic mechanisms of disulfiram and copper(ii) in cancer cells

Patricia Erebi Tawari,†^a Zhipeng Wang,†^a Mohammad Najlah,^b Chi Wai Tsang,^c Vinodh Kannappan,^a Peng Liu,^a Christopher McConville,^e Bin He,^d Angel L. Armesilla^a and Weiguang Wang*^a

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^a Research Institute in Healthcare Science, Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK
E-mail: w.wang2@wlv.ac.uk
Fax: +44 (0)1902 322714
Tel: +44 (0)1902 322756

^b Medicine & Healthcare Science, Faculty of Medical Science, Anglia Ruskin University, UK

^c School of Chemistry, University of Birmingham, UK

^d National Engineering Res Centre for Biomaterials, Sichuan University, China

^e School of Pharmacy, Faculty of Science & Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK

Abstract

The anticancer activity of disulfiram (DS) is copper(II) (Cu)-dependent. This study investigated the anticancer mechanisms of DS/Cu using in vitro cytotoxicity and metabolic kinetic analysis. Our study indicates that DS/Cu targets cancer cells by the combination of two types of actions: (1) instant killing executed by DS/Cu reaction generated reactive oxygen species; (2) delayed cytotoxicity introduced by the end product, DDC-Cu. Nanoencapsulation of DS might shed light on repositioning of DS into cancer treatment.

Toxicology Research

The cytotoxic mechanisms of disulfiram and copper(ii) in cancer cells

Abstract

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