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Thiostrepton as a Potential Therapeutic Agent for Hepatocellular Carcinoma.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Sep 08; Vol. 25 (17). Date of Electronic Publication: 2024 Sep 08. - Publication Year :
- 2024
-
Abstract
- Due to limited drug efficacy and drug resistance, it is urgent to explore effective anti-liver cancer drugs. Repurposing drugs is an efficient strategy, with advantages including reduced costs, shortened development cycles, and assured safety. In this study, we adopted a synergistic approach combining computational and experimental methods and identified the antibacterial drug thiostrepton (TST) as a candidate for an anti-liver cancer drug. Although the anti-tumor capabilities of TST have been reported, its role and underlying mechanisms in hepatocellular carcinoma (HCC) remain unclear. TST was found here to inhibit the proliferation of HCC cells effectively, arresting the cell cycle and inducing cell apoptosis, as well as suppressing the cell migration. Further, our findings revealed that TST induced mitochondrial impairment, which was demonstrated by destroyed mitochondrial structures, reduced mitochondria, and decreased mitochondrial membrane potential (MMP). TST caused the production of reactive oxygen species (ROS), and the mitochondrial impairment and proliferation inhibition of HCC cells were completely restored by the ROS scavenger N-acetyl-L-cysteine (NAC). Moreover, we discovered that TST induced mitophagy, and autophagy inhibition effectively promoted the anti-cancer effects of TST on HCC cells. In conclusion, our study suggests TST as a promising candidate for the treatment of liver cancers, and these findings provide theoretical support for the further development and potential application of TST in clinical liver cancer therapy.
- Subjects :
- Humans
Cell Line, Tumor
Mitochondria drug effects
Mitochondria metabolism
Antineoplastic Agents pharmacology
Antineoplastic Agents therapeutic use
Cell Movement drug effects
Mitophagy drug effects
Autophagy drug effects
Carcinoma, Hepatocellular drug therapy
Carcinoma, Hepatocellular pathology
Carcinoma, Hepatocellular metabolism
Liver Neoplasms drug therapy
Liver Neoplasms pathology
Liver Neoplasms metabolism
Thiostrepton pharmacology
Thiostrepton therapeutic use
Cell Proliferation drug effects
Reactive Oxygen Species metabolism
Apoptosis drug effects
Membrane Potential, Mitochondrial drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39273665
- Full Text :
- https://doi.org/10.3390/ijms25179717