Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
2.
Nat Commun ; 10(1): 4731, 2019 10 21.
Article in English | MEDLINE | ID: mdl-31636264

ABSTRACT

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.


Subject(s)
Apoptosis/drug effects , Cardiac Glycosides/pharmacology , Cellular Senescence/drug effects , Chondrocytes/drug effects , Fibroblasts/drug effects , A549 Cells , Animals , Antibiotics, Antineoplastic/pharmacology , Bleomycin/pharmacology , Breast Neoplasms , Cell Line, Tumor , Cell Membrane/drug effects , Digoxin/pharmacology , Female , Humans , Hydrogen-Ion Concentration/drug effects , Mice , Osteoarthritis , Ouabain/pharmacology , Proscillaridin/pharmacology , Pulmonary Fibrosis , Xenograft Model Antitumor Assays
SELECTION OF CITATIONS
SEARCH DETAIL
...