Identification and characterization of Digoxin as a novel senolytic drug

Abstract

Cellular senescence is a potent protective response against several potentially dangerous stimuli that prevent the progression of damaged cells by inducing a stable proliferative arrest. In this way, cancer cells need to avoid this response in order to grow and form tumors. However, in recent years it has been described that senescent cells remain active and secrete a large number of factors to their environment with antagonistic activities. In some cases, these factors may have a reinforcing effect on senescence, but in other cases they may have a protumoral activity. For this reason, new approaches have been emerged to specifically eliminate these senescent cells by using senolytics. In this thesis, we performed a high-throughput screening of a chemical library to identify novel senolytic compounds. In this way, we identified the family of Cardiac Glycosides, and in particular Digoxin, as a promising senolytic drug. We also characterized the potential mechanisms behind the senolytic effect of Digoxin.