The disulfiram/copper complex induces apoptosis and inhibits tumour growth in human osteosarcoma by activating the...

Area of Science:

• Oncology
• Pharmacology
• Drug Repurposing

Background:

• Drug discovery is costly and time-consuming, making drug repositioning an attractive alternative, especially for cancer therapies.
• Disulfiram (DSF), an alcoholism drug, demonstrates anticancer potential and enhances chemotherapy efficacy.
• Combining DSF with copper may offer a more potent therapeutic approach.

Purpose of the Study:

• To investigate the efficacy and safety of the disulfiram/copper (DSF/Cu) complex against human osteosarcoma (OS).
• To explore the underlying mechanisms of DSF/Cu's anti-cancer effects in OS.

Main Methods:

• In vitro studies on OS cell lines assessing proliferation, clonogenicity, reactive oxygen species (ROS) generation, cell cycle arrest, autophagy, and apoptosis.
• In vivo studies using a xenograft model to evaluate tumor growth inhibition and organ toxicity.
• Exploration of the ROS/JNK pathway's role in DSF/Cu-induced apoptosis.

Main Results:

• DSF/Cu significantly inhibited OS cell proliferation and clonogenicity.
• DSF/Cu induced ROS generation, leading to cell cycle arrest, autophagy, and apoptosis in an ROS-dependent manner.
• DSF/Cu demonstrated significant OS tumor growth inhibition in vivo with low organ toxicity.

Conclusions:

• The DSF/Cu complex effectively inhibits osteosarcoma growth through ROS-mediated apoptosis via the ROS/JNK pathway.
• DSF/Cu presents a potential safe and efficient therapeutic option for clinical osteosarcoma treatment.
• Drug repositioning of DSF with copper is a viable strategy for developing novel osteosarcoma therapies.