Oxidized Disulfiram Derivatives Activate an Integrated Stress Response and Cause Paraptosis of Human Cancer Cells BT474

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Abstract

Disulfiram, a well-known anti-alcohol drug with minimal side effects, as well as other dithiocarbamates are being investigated as part of the Drug Repurposing program in order to expand their use, including in oncology. In this work, using the example of human tumor cells BT474, it was found that the action of oxidized disulfiram metabolites generated by aerobic oxidation of diethyldithiocarbamate in the presence of the catalyst cobalamin (vitamin B12b) causes stress in the endoplasmic reticulum, and the integrated stress leads to cell death by paraptosis. The ability of substances of this class to cause non-apoptotic types of cell death is of interest for the development of new approaches in oncotherapy.

About the authors

M. E Solovieva

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: ms0@mail.ru
Pushchino, Russia

I. V Odinokova

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Pushchino, Russia

Yu. V Shatalin

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences; Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences

Pushchino, Russia; Moscow, Russia

A. A Mishukov

Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences

Moscow, Russia

E. L Holmuhamedov

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences; Samarkand International Technological University

Pushchino, Russia; Samarkand, Uzbekistan

V. S Akatov

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences

Pushchino, Russia

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