Disulfiram

Disulfiram is a copper chelator and an irreversible inhibitor of aldehyde dehydrogenase (ALDH; IC₅₀ = 0.1 mM).¹ It increases the production of reactive oxygen species (ROS) when used at a concentration of 250 nM, as well as increases NF-κB protein levels and reduces neurosphere formation in U87MG glioblastoma multiforme cells at 1 µM.² Disulfiram (50 mg/kg per day) decreases tumor growth, inhibits proteasome activity, and induces apoptosis in an MDA-MB-231 breast cancer mouse xenograft model.³ Formulations containing disulfiram have been used in the treatment of alcohol dependence.

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1. Kraemer, R.J., and Deitrich, R.A. Isolation and characterization of human liver aldehyde dehydrogenase. The Journal of Biological Chemisty 243(24), 6402-6408 (1968).

2. Liu, P., Brown, S., Goktug, T., et al. Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. Br. J. Cancer 107(9), 1488-1497 (2012).

3. Chen, D., Cui, Q.C., Yang, H., et al. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res. 66(21), 10425-10433 (2006).