Cited 4 time in webofscience Cited 3 time in scopus

Identification of SYK inhibitor, R406 as a novel senolytic agent

Title
Identification of SYK inhibitor, R406 as a novel senolytic agent
Authors
Cho, Hyun-JiYang, Eun JaePark, Joon TaeKim, Jae-RyongKim, Eok-CheonJung, Kyong-JinPark, Sang ChulLee, Young-Sam
DGIST Authors
Cho, Hyun-Ji; Lee, Young-Sam
Issue Date
2020-05
Citation
Aging-US, 12(9), 8221-8240
Type
Article
Article Type
Article
Author Keywords
cellular senescencesenolyticsapoptosisFAKp38
Keywords
ACTIVATED PROTEIN-KINASEFOCAL ADHESION KINASESENESCENT CELLSCLEARANCEAPOPTOSISTARGETGROWTHPROLIFERATIONTRIGGERSPATHWAYS
ISSN
1945-4589
Abstract
The selective removal of senescent cells by senolytics is suggested as a potential approach to reverse aging and extend lifespan. Using high-throughput screening with replicative senescence of human diploid fibroblasts (HDFs), we identified a novel senolytic drug R406 that showed selective toxicity in senescent cells. Using flow cytometry and caspase expression analysis, we confirmed that R406 caused apoptotic cell death along with morphological changes in senescent cells. Interestingly, R406 altered the cell survival-related molecular processes including the inhibition of phosphorylation of the focal adhesion kinase (FAK) and p38 mitogen-activated protein kinase (MAPK) in senescent cells. This pattern was not observed in other known senolytic agent ABT263. Correspondingly, apoptotic cell death in senescent cells was induced by simultaneously blocking the FAK and p38 pathways. Taken together, we suggest that R406 acts as a senolytic drug by inducing apoptosis and reducing cell attachment capacity. © Cho et al.
URI
http://hdl.handle.net/20.500.11750/11893
DOI
10.18632/aging.103135
Publisher
Impact Journals
Related Researcher
  • Author Lee, Young-Sam Senescence-Associated Mechanism Lab
  • Research Interests DNA replication and repair; Restoration of cellular senescence; Structural and functional relationship of proteins
Files:
Collection:
Division of Biotechnology1. Journal Articles
Department of New BiologySenescence-Associated Mechanism Lab1. Journal Articles


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