The effect of didox on the induction of cell death in lung cancer cells challenged with SARS-CoV 2 recombinant spike proteins

Abstract

Lung cancer still accounts for most deaths caused by cancer in South Africa. Patients with lung cancer are more susceptible to coronavirus disease 2019 (COVID-19) fatal consequences due to their reduced lung function and immunosuppression. The COVID-19 causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2), is highly transmissible, and upon infection it triggers an inflammatory cytokine storm, consequently causing organ or tissue damage. Various therapeutics have been researched for the development of effective anti-cancer and anti-inflammatory treatment to counteract effects caused by COVID-19 on cancer patients. Didox, a ribonucleotide reductase inhibitor, is a potential therapeutic agent with anti-cancer, anti-viral and anti-inflammatory properties. Therefore, the study was aimed at determining the effects that Didox has on lung cancer cells that were exposed to SARS-CoV 2 recombinant spike proteins. To achieve this aim, the antioxidant activity of Didox was determined using DPPH and FRAP assays, while viability, morphology, nuclear integrity, induction of apoptosis and oxidative stress in A549 lung cancer cells were determined using the MTT assay, light microscopy, nitric oxide assay, annexin V and PI assay, and oxidative stress assay, respectively. Both the DPPH and FRAP assay revealed the free radical scavenging properties and ferric reducing power properties of Didox, observed in a concentration-dependent manner, respectively. Didox reduced the nitric oxide production induced by SARS-CoV 2 spike proteins and the same effect was observed on ROS induced by SARS-CoV 2 in A549 lung cancer cells. A decreased population of A549 cells and cell shrinkage was observed with an increase in concentration of Didox in a time-dependent manner. The cytotoxicity assay showed that the viability of the A549 decreased with an increase in concentration of Didox. The population of apoptotic cells increased with exposure of A549 cells to SARS-CoV 2 and Didox, showing that Didox accelerated SARS-CoV 2 induced an inflammation-mediated cell death. In conclusion, Didox exerted a cytostatic effect on A549 cells and also reduced the oxidative stress induced by SARS-CoV 2 recombinant spike proteins in A549 cells. Thus, these antioxidant properties render Didox a potential therapeutic candidate for further research in the development of cancer and COVID-19 treatment options.