Abstract
Purpose
Anti-helmintic drugs mebendazole and albendazole are commonly used to treat a variety of parasitic infections. They have recently shown some promising results in pre-clinical in vitro and in vivo anti-cancer studies.
Methods
We compare their efficacy in breast and colon cancer cell lines as well as in non-cancerous cells and elucidate their mechanism of action. The drugs were screened for cytotoxicity in MDA-MB-231, MCF-7 (breast cancer), HT-29 (colorectal cancer), and mesenchymal stromal cells, using the MTT assay. Their effects on the cell cycle, tubulin levels, and cell death mechanisms were analysed using flow cytometry and fluorescent microscopy.
Results
Mebendazole and albendazole were found to selectively kill cancer cells, being most potent in the colorectal cancer cell line HT-29, with both drugs having IC50 values of less than 1 µM at 48 h. Both mebendazole and albendazole induced classical apoptosis characterised by caspase-3 activation, phosphatidylserine exposure, DNA fragmentation, mitochondrial membrane permeability, and reactive oxygen species production. Cell cycle arrest in the G2/M phase was found, and tubulin polymerisation was disrupted.
Conclusion
Mebendazole and albendazole were shown to cause selective cancer cell death via a mechanism of classical apoptosis and cell cycle arrest, involving the destabilisation of microtubules.
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All data are available from the corresponding author upon reasonable request.
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Acknowledgements
We acknowledge funding from the Department of Pharmacology and Toxicology, University of Otago.
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This research was supported by the Department of Pharmacology and Toxicology, School of Biomedical Sciences, University of Otago.
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SKB designed the study and experiments and prepared the manuscript, JSSMP carried out the experiments and the data analysis and contributed to the manuscript.
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Petersen, J.S.S.M., Baird, S.K. Treatment of breast and colon cancer cell lines with anti-helmintic benzimidazoles mebendazole or albendazole results in selective apoptotic cell death. J Cancer Res Clin Oncol 147, 2945–2953 (2021). https://doi.org/10.1007/s00432-021-03698-0
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DOI: https://doi.org/10.1007/s00432-021-03698-0