Advancing Cancer Therapy with Copper/Disulfiram Nanomedicines and Drug Delivery Systems

Author:

Kang Xuejia12ORCID,Jadhav Sanika3ORCID,Annaji Manjusha1,Huang Chung-Hui1,Amin Rajesh1,Shen Jianzhong1,Ashby Charles R.4,Tiwari Amit K.5ORCID,Babu R. Jayachandra1ORCID,Chen Pengyu2ORCID

Affiliation:

1. Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA

2. Materials Research and Education Center, Materials Engineering, Department of Mechanical Engineering, Auburn University, Auburn, AL 36849, USA

3. Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA

4. Department of Pharmaceutical Sciences, College of Pharmacy, St. John’s University, Queens, NY 11431, USA

5. Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA

Abstract

Disulfiram (DSF) is a thiocarbamate based drug that has been approved for treating alcoholism for over 60 years. Preclinical studies have shown that DSF has anticancer efficacy, and its supplementation with copper (CuII) significantly potentiates the efficacy of DSF. However, the results of clinical trials have not yielded promising results. The elucidation of the anticancer mechanisms of DSF/Cu (II) will be beneficial in repurposing DSF as a new treatment for certain types of cancer. DSF’s anticancer mechanism is primarily due to its generating reactive oxygen species, inhibiting aldehyde dehydrogenase (ALDH) activity inhibition, and decreasing the levels of transcriptional proteins. DSF also shows inhibitory effects in cancer cell proliferation, the self-renewal of cancer stem cells (CSCs), angiogenesis, drug resistance, and suppresses cancer cell metastasis. This review also discusses current drug delivery strategies for DSF alone diethyldithocarbamate (DDC), Cu (II) and DSF/Cu (II), and the efficacious component Diethyldithiocarbamate–copper complex (CuET).

Funder

National Institutes of Health

Publisher

MDPI AG

Subject

Pharmaceutical Science

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