Niclosamide: drug repurposing for human chondrosarcoma treatment via the caspase-dependent mitochondrial apoptotic
Qing-Shuai Yu1, Hao-Ran Xin2, Rong-Lin Qiu2
1Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010, China.
Abstract:
Poor sensitivity to chemotherapy drugs and high recurrence rates are the bottlenecks to successful chondrosarcoma treatment. Notably, niclosamide has been identified as a potential anti-cancer agent. To investigate the effects and mechanisms of niclosamide in the context of human chondrosarcoma treatment, SW1353 and CAL78 human chondrosarcoma cells were treated with various concentrations of niclosamide. The CKK-8 assay was performed to quantify cell viability. Cell proliferation was determined with crystal violet staining and colony forming assays. TUNEL and annexin V-FITC flow cytometry assays were performed to detect cell apoptosis. Wound healing and Transwell assays were conducted to evaluate migratory and invasive cell behaviors. The effect of niclosamide on the mitochondria was evaluated with the JC-1 and Seahorse Cell Mito Stress Assays. The expression of caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, and β-tubulin levels were investigated by western blotting. Collectively, the data demonstrated that niclosamide inhibited cell growth and proliferation, attenuated migratory and invasive cell behaviors, and promoted apoptosis. Niclosamide is as a potent chondrosarcoma tumor inhibitor that activates the caspase-dependent mitochondrial apoptotic pathway and could be a novel therapeutic approach to treat chondrosarcoma.
Insights
Niclosamide effectively inhibits chondrosarcoma cell growth and spread by triggering programmed cell death. This study highlights niclosamide as a promising therapeutic agent for treating chondrosarcoma, a challenging bone cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Chondrosarcoma treatment faces challenges due to poor chemotherapy sensitivity and high recurrence rates.
- Niclosamide, an anti-parasitic drug, shows potential as an anti-cancer agent.
Purpose of the Study:
- To investigate the anti-cancer effects and underlying mechanisms of niclosamide on human chondrosarcoma cells.
- To evaluate niclosamide's potential as a novel therapeutic strategy for chondrosarcoma.
Main Methods:
- Cell viability, proliferation, apoptosis, migration, and invasion assays were performed on chondrosarcoma cell lines treated with niclosamide.
- Mitochondrial function was assessed using JC-1 and Seahorse assays.
- Western blotting was used to analyze key protein expressions involved in apoptosis and cell structure.
Main Results:
- Niclosamide significantly inhibited chondrosarcoma cell growth, proliferation, migration, and invasion.
- The drug treatment promoted significant apoptosis in cancer cells.
- Niclosamide treatment affected mitochondrial function and activated the caspase-dependent apoptotic pathway.
Conclusions:
- Niclosamide demonstrates potent anti-tumor activity against human chondrosarcoma cells.
- The drug functions by activating the caspase-dependent mitochondrial apoptotic pathway.
- Niclosamide represents a potential novel therapeutic approach for chondrosarcoma treatment.
