ABSTRACT
Selenium has been extensively evaluated clinically as a chemopreventive agent with variable results depending on the type and dose of selenium used. Selenium species are now being therapeutically evaluated as modulators of drug responses rather than as directly cytotoxic agents. In addition, recent data suggest an association between selenium base-line levels in blood and survival of patients with COVID-19. The major focus of this mini review was to summarize: the pathways of selenium metabolism; the results of selenium-based chemopreventive clinical trials; the potential for using selenium metabolites as therapeutic modulators of drug responses in cancer (clear-cell renal-cell carcinoma (ccRCC) in particular); and selenium usage alone or in combination with vaccines in the treatment of patients with COVID-19. Critical therapeutic targets and the potential role of different selenium species, doses, and schedules are discussed.
Subject(s)
COVID-19 Drug Treatment , Neoplasms/drug therapy , Selenium/therapeutic use , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , COVID-19/virology , DNA Repair/drug effects , Drug Resistance, Neoplasm/drug effects , Humans , NF-E2-Related Factor 2/chemistry , NF-E2-Related Factor 2/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Selenium/chemistry , Selenium/metabolism , Selenium/pharmacologySubject(s)
COVID-19 Drug Treatment , Coronavirus 3C Proteases/antagonists & inhibitors , Oleanolic Acid/analogs & derivatives , SARS-CoV-2/enzymology , Antiviral Agents/chemistry , COVID-19/enzymology , COVID-19/virology , Computational Chemistry , Coronavirus 3C Proteases/chemistry , Drug Repositioning , Humans , NF-E2-Related Factor 2/agonists , NF-E2-Related Factor 2/chemistry , Oleanolic Acid/chemistry , Protease Inhibitors/chemistry , Protease Inhibitors/therapeutic use , SARS-CoV-2/pathogenicity , Virus Replication/drug effectsABSTRACT
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 overstimulation often occurs in tumour cells and a complex correlation of Nrf2 with cancer initiation and progression has been widely described. Therefore, if on one hand, Nrf2 has a dual role in cancer, on the other hand, the factor seems to display a univocal function in preventing inflammation and cytokine storm that occur under viral infections, specifically in coronavirus disease 19 (COVID-19). In such a variegate context, the present review aims to dissect the roles of Nrf2 in both cancer and COVID-19, two widespread diseases that represent a cause of major concern today. In particular, the review describes the molecular aspects of Nrf2 signalling in both pathological situations and the most recent findings about the advantages of Nrf2 inhibition or activation as possible strategies for cancer and COVID-19 treatment respectively.