Repositioning an Old Anti-Alcoholism Drug: Disulfiram as a Selective, Effective and Economical Anticancer Agent

Claire Soave,Maricela Viola Rhenals

doi:10.4172/2329-6631.1000e147

Claire Soave, Maricela Viola Rhenals

Open Access

https://doi.org/10.4172/2329-6631.1000e147

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Abstract

Disulfiram (tetra ethyl thiuram disulfide, or DSF), is a disulfide derivative of N, N-diethyl dithiocarbamate (DEDTC). DSF is an FDA approved drug for the treatment of alcoholism, and at low doses continues to be a useful treatment option for those suffering from the disease. DSF is a member of the dithiocarbamate family, and is thus a metal chelator. Many cancer cells have elevated levels of copper, a metal to which DSF can bind. Thus, DSF is of great interest in cancer research as an antitumor agent, as studies suggest the DSF-copper complex may be cytotoxic to cancer cells. This could allow for targeting of some types of cancer cells with elevated copper levels by DSF.

Highlights

Disulfiram, is a disulfide derivative of N, N-diethyl dithiocarbamate (DEDTC) that has been used since the 19th century in the manufacturing of rubber
It has been shown that some compounds containing copper can inhibit the 26S proteasome activity in tumor cells, leading to apoptosis induction
This complex is formed in order to stabilize metal ions with unusually high or low oxidation states like copper (II), iron (III), cadmium (II), and zinc (II), which are stable depending on their resonance forms and the delocalization of the positive charge from the metal atom to the periphery of the complex [6,7,8,9,10,11,12,13,14,15]. This delocalization of electrons causes a variety of different cellular responses. One of these is an altered cellular redox environment, inducing different ROSdependent pathways such as inhibition of NF-κB, alterations in expression of antioxidant enzymes such as catalase and manganese superoxide dismutase or copper/zinc superoxide dismutase, and altered localization of proteins related to intrinsic apoptotic pathways like BAX, Bcl-2, BAD and cytochrome C

Summary

Introduction

Disulfiram (tetraethylthiuram disulfide, or DSF), is a disulfide derivative of N, N-diethyl dithiocarbamate (DEDTC) that has been used since the 19th century in the manufacturing of rubber. Since cells from many different types of cancer have been found to have abnormally high levels of copper, researchers aimed to see whether this could be used as a target when treating with DSF in an effort to inhibit the proteasome. Researchers treated two breast cancer cell lines and one normal breast cell line with DSF and found that in the two malignant lines, chymotrypsin-like proteasomal activity was inhibited.

Results

Conclusion