New uses for old copper-binding drugs: converting the pro-angiogenic copper to a specific cancer cell death inducer

Abstract

Background: The conventional approach toward anticancer drug development is a time-consuming and expensive procedure. Objective/methods: One approach to expedite this process and achieve more affordable means is to discover new applications of existing drugs, since their pharmacokinetics and pharmacological profiles are well known. Results: Our encouraging findings in recent studies reveal anticancer activities of several copper-binding ligands including disulfiram (an antialcoholism drug), clioquinol (used to treat Alzheimer's and Huntington's diseases) and diethyldithiocarbamate (an agent for HIV-1 infection treatment). Conclusion: These in vitro and in vivo studies have demonstrated that these archaic drugs can target and react with tumor cellular copper, forming complexes that act as potent proteasome inhibitors and apoptosis inducers.

Keywords::

• Antitumor activity
• clioquinol
• copper
• disulfiram
• dithiocarbamate
• proteasome inhibitors

Acknowledgements

The authors thank Carol Maconochie, Vesna Milacic, Michael Frezza and Huanjie Yang for critical reading of the manuscript.

Notes