The cytotoxic and antitumoral effects of Remdesivir, an antiviral RdRp inhibitor, on different cancer cells in vitro


Eryılmaz I. E., Bergel C. C., Egeli Ü., Çeçener G.

MOLECULAR & CELLULAR TOXICOLOGY, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2023
  • Doi Number: 10.1007/s13273-023-00379-6
  • Journal Name: MOLECULAR & CELLULAR TOXICOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Food Science & Technology Abstracts
  • Keywords: Remdesivir, Cancer, Cytotoxic effect, Apoptosis, Autophagy, Cell death, ANTICANCER, AUTOPHAGY, DRUGS
  • Bursa Uludag University Affiliated: Yes

Abstract

BackgroundPrevious 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.ObjectiveWe 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.ResultsRem treatment at 10, 25, and 50 & mu;M 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.ConclusionsOur 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.