Characterization of the HDAC/PI3K inhibitor CUDC-907 as a novel senolytic

• DOI: 10.18632/aging.204616
• Publication Date: 2023-04-16T01:23:40Z
• Authors: Fares Al-Mansour; Abdullah Alraddadi; Buwei He; Anes Saleh; Marta Poblocka; Wael Alzahrani; Shaun Cowley; Salvador Macip
• Keywords: Senescence

The accumulation of senescent cells has an important role in the phenotypical changes observed ageing and many age-related pathologies. Thus, strategies designed to prevent these effects, collectively known as senotherapies, have a strong clinical potential. Senolytics are type senotherapy aimed at specifically eliminating from tissues. Several small molecule compounds with senolytic properties already been identified, but their specificity range action variable. Because this, potential novel senolytics being actively investigated. Given involvement HDACs PI3K pathway senescence, we hypothesized that dual inhibitor CUDC-907, drug trials for its antineoplastic could effects. Here, show CUDC-907 was indeed able selectively induce apoptosis driven senesce by p53 expression, not when senescence happened absence p53. Consistent showed different models stress-induced senescence. Our results also indicate functions depend on inhibitory effects both PI3K, which leads increase reduction BH3 pro-survival proteins. Taken together, our be clinically relevant pathological conditions is involved.