Abstract
Background
Previous studies have shown similarities in the metabolism of cancer cells and parasites, suggesting that antiparasitic drugs may be used as anticancer agents. Remdesivir (Rem), an RdRp inhibitor, has been recently used in SARS-CoV-2 pandemic. Although the apoptotic effect of Rem has been demonstrated on the SKOV3 ovarian cancer cell line, its cytotoxic effect has not been analyzed in different cancer cells.
Objective
We aimed to evaluate its cell death-inducing effects on PC3 prostate cancer, HepG2 hepatocellular carcinoma, and A2058 malignant melanoma cells for the first time, using WST-1, Annexin V, cell cycle analysis, AO/EB staining, live-cell imaging, TEM, and gene expression analysis.
Results
Rem treatment at 10, 25, and 50 µM significantly decreased cell viability in all cancer cells (p < 0.01). While Rem triggered apoptosis in PC3, vacuole-dependent cell death was detected in HepG2 cells by visualizing the cells with TEM and time-dependent live-cell imaging. Moreover, both forms of cell death were triggered together in A2058. The formation of AVOs were observed more after 12 h and 24 h in HepG2 and A2058 cells, respectively. Additionally, Rem significantly induced cell cycle arrest in the G2/M (p < 0.01). Finally, the mRNA levels of autophagic markers, Atg12, Atg5, p62, Beclin, and LC3, were significantly increased in A2058 and HepG2 (p < 0.01) compared to control groups.
Conclusions
Our results suggest that Rem has promising cytotoxic effects on various cancer cells. However, it triggers different types of cell death in different cancer types, indicating that further studies should focus on clarifying the molecular mechanism of the specific action of Rem.
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Data availability
All data are available in the manuscript.
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This research was supported by the Bursa Uludag University Scientific Research Project Coordination Unit. Project Number: THIZ-2021–599.
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IEE, CCB designed and performed the experiments. IEE, CCB, UE analyzed and interpreted data, and performed statistical analysis. IEE, CCB wrote the main manuscript text. UE, GC revised the manuscript. All authors reviewed the manuscript.
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Author Isil Ezgi Eryilmaz declares that she has no conflict of interest. Author Ceyda Colakoglu Bergel declares that she has no conflict of interest. Author Unal Egeli declares that he has no conflict of interest. Author Gulsah Cecener declares that she has no conflict of interest.
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Eryilmaz, I.E., Bergel, C.C., Egeli, U. et al. The cytotoxic and antitumoral effects of Remdesivir, an antiviral RdRp inhibitor, on different cancer cells in vitro. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00379-6
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DOI: https://doi.org/10.1007/s13273-023-00379-6