Title:Disulfiram's Anticancer Activity: Evidence and Mechanisms
Volume: 16
Issue: 11
Author(s): Yang Jiao, Bethany N. Hannafon and Wei-Qun Ding
Affiliation:
Keywords:
Disulfiram, cancer, cancer stem cells, ALDH, adjuvant chemotherapy, oxidative stress.
Abstract: Disulfiram (DSF), a derivative of thiuram, has been used in humans to treat
alcoholism for more than 60 years. Over the past decade, however, increasing evidence indicates
that DSF possesses a great potential for the treatment of human cancers. DSF’s anticancer
activity has been demonstrated in both in vitro and in vivo model systems, and has been tested in
human clinical trials for various cancer types. It is also evident that DSF can sensitize tumor
cells to radiotherapy and enhance the cytotoxicity of anticancer drugs, thus DSF may serve as an
adjuvant therapy. The key to DSF’s anticancer action relates to its ability to suppress cancer
stem cells by targeting aldehyde dehydrogenase (ALDH), a marker of cancer stem cells, and
inhibit proteasome activity in cancer cells by forming complexes with metal ions. In addition,
DSF targets epigenetic mechanisms and modulates cellular signaling pathways to slow down
tumor progression. DSF also induces apoptosis, inhibits cancer cell proliferation, and suppresses
cancer cell metastasis. Considering that the pharmacokinetics of DSF are well-established and a
safety profile has been recorded, this compound is an attractive “old” drug that has great potential for rapid
development into a new cancer therapeutic. This article provides a brief review of the history of DSF use in humans,
evidence for its anticancer activities, the molecular mechanisms of DSF action that have been illustrated by recent
studies, and the potential for repurposing DSF as a new chemotherapeutic drug in the near future.
