Affiliation:
1. Department of Orthopaedics, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, No. 100, Hai Ning Road, Shanghai 200080, China
2. Department of Orthopedic Surgery, Chongqing University Central Hospital, Chongqing 400000, China
Abstract
Abstract
Given the huge cost, long research and development (R&D) time and uncertain side effects of discovering new drugs, drug repositioning of those approved to treat diseases clinically as new drugs for other pathological conditions, especially cancers, is a potential alternative strategy. Disulfiram (DSF), an old drug used to treat alcoholism, has been found to exhibit anticancer activity and improve chemotherapeutic efficacy in cancers by an increasing number of studies. In addition, the combination of DSF and copper may be a more effective therapeutic strategy. In this study, we report the toxicity of the disulfiram/copper (DSF/Cu) complex to human osteosarcoma (OS) both in vitro and in vivo. DSF/Cu significantly inhibited the proliferation and clonogenicity of OS cell lines. Furthermore, the generation of reactive oxygen species (ROS) was triggered by DSF/Cu, and cell arrest, autophagy and apoptosis were induced in an ROS-dependent manner. The underlying mechanism of this process was explored, and DSF/Cu may mainly inhibit OS by inducing apoptosis by activating the ROS/JNK pathway. DSF/Cu also inhibited OS growth in a xenograft model with low levels of organ-related toxicities. These results suggest that the DSF/Cu complex could be an efficient and safe option for the treatment of OS in the clinic.
Funder
Shanghai Natural Science Foundation
Shanghai Sailing Program
Shanghai Jiaotong University Translation Medicine Cross Research Fund
Doctoral Innovation Fund of Shanghai Jiaotong University School of Medicine
Publisher
Oxford University Press (OUP)
Subject
Molecular Biology,Biochemistry,General Medicine
Cited by
13 articles.
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