2019/10/21 by Francisco Triana-Martínez, Pilar Picallos-Rabina, Sabela Da Silva‐Álvarez +24 · 2 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Advanced biosensing and bioanalysis techniques #Biochemistry #Biology #Cancer research #Cardiac glycoside #Cell biology #Chemistry #Cytotoxicity #Genetics #Identification (biology) #In vitro #In vivo #Medicine #Ouabain #Pharmacology #RNA Interference and Gene Delivery #Senescence #Telomeres, Telomerase, and Senescence
paper · pdf · doi:10.1038/s41467-019-12888-x
openalex publication_date 2019/10/21 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04
Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification. Senescent cells present a slightly depolarized plasma membrane and higher concentrations of H+, making them more susceptible to the action of CGs. These vulnerabilities can be exploited for therapeutic purposes as evidenced by the in vivo eradication of tumors xenografted in mice after treatment with the combination of a senogenic and a senolytic drug. The senolytic effect of CGs is also effective in the elimination of senescence-induced lung fibrosis. This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases.