{"id":"doi:10.18632/aging.101100","kind":"article","title":"Discovery of piperlongumine as a potential novel lead for the development of senolytic agents","authors":["Wang Y","Chang J","Liu X","Zhang X","Zhang S","Zhou D","Zheng G"],"author_count":7,"year":2016,"published":"2016-11-01","venue":"Aging","cited_by":214,"doi":"10.18632/aging.101100","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.18632/aging.101100","archive_url":"https://space-kitty.com/papers/doi:10.18632/aging.101100","updated":null,"pmid":"27913811","pmcid":"PMC5191878","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC5191878/pdf","abstract":"Accumulating evidence indicates that senescent cells play an important role in many age-associated diseases. The pharmacological depletion of senescent cells (SCs) with a \"senolytic agent\", a small molecule that selectively kills SCs, is a potential novel therapeutic approach for these diseases. Recently, we discovered ABT-263, a potent and highly selective senolytic agent, by screening a library of rationally-selected compounds. With this screening approach, we also identified a second senolytic agent called piperlongumine (PL). PL is a natural product that is reported to have many pharmacological effects, including anti-tumor activity. We show here that PL preferentially killed senescent human WI-38 fibroblasts when senescence was induced by ionizing radiation, replicative exhaustion, or ectopic expression of the oncogene Ras . PL killed SCs by inducing apoptosis, and this process did not require the induction of reactive oxygen species. In addition, we found that PL synergistically killed SCs in combination with ABT-263, and initial structural modifications to PL identified analogs with improved potency and/or selectivity in inducing SC death. Overall, our studies demonstrate that PL is a novel lead for developing senolytic agents.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Discovery of piperlongumine as a potential novel lead for the development of senolytic agents\" by Wang Y, Chang J, Liu X et al., https://doi.org/10.18632/aging.101100, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"aging-longevity","name":"Biology of Aging & Longevity","domain_slug":"medicine"}],"cited_in_dossiers":[]}