Journal article

The antimalarial drug mefloquine enhances TP53 premature termination codon readthrough by aminoglycoside G418

Michael W Ferguson, Chloe AN Gerak, Christalle CT Chow, Ettore J Rastelli, Kyle E Elmore, Florian Stahl, Sara Hosseini-Farahabadi, Alireza Baradaran-Heravi, Don M Coltart, Michel Roberge

PLoS One | PUBLIC LIBRARY SCIENCE | Published : 2019

Abstract

Nonsense mutations constitute ~10% of TP53 mutations in cancer. They introduce a premature termination codon that gives rise to truncated p53 protein with impaired function. The aminoglycoside G418 can induce TP53 premature termination codon readthrough and thus increase cellular levels of full-length protein. Small molecule phthalimide derivatives that can enhance the readthrough activity of G418 have also been described. To determine whether readthrough enhancers exist among drugs that are already approved for use in humans, we tested seven antimalarial drugs for readthrough of the common R213X TP53 nonsense mutation in HDQ-P1 breast cancer cells. Mefloquine induced no TP53 readthrough act..

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University of Melbourne Researchers

Grants

Awarded by Canadian Cancer Society


Awarded by Michael Smith Foundation for Health Research


Awarded by National Science Foundation


Awarded by Welch Foundation


Funding Acknowledgements

This work was supported by: MR, Canadian Cancer Society grant 704700, http://www.cancer.ca/research and the Michael Smith Foundation for Health Research grant 17224, https://www.msfhr.org; DMC: National Science Foundation grant NSF 1300652, https://www.nsf.gov/, the Welch Foundation grant E-1806, www.welch1. org and the University of Houston, www.uh.edu.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.