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Tubeimoside-1 Enhances TRAIL-Induced Apoptotic Cell Death through STAMBPL1-Mediated c-FLIP Downregulation

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Author(s)
So Rae SongSeung Un SeoSeon Min WooJi Yun YoonSimmyung YookTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Int J Mol Sci
Issued Date
2023
Volume
24
Issue
14
Keyword
STAMBPL1TBMS-1TRAILc-FLIPdeubiquitinase
Abstract
Tubeimoside-1 (TBMS-1), a traditional Chinese medicinal herb, is commonly used as an anti-cancer agent. In this study, we aimed to investigate its effect on the sensitization of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Our results revealed that even though monotherapy using TBMS-1 or TRAIL at sublethal concentrations did not affect cancer cell death, combination therapy using TBMS-1 and TRAIL increased apoptotic cell death. Mechanistically, TBMS-1 destabilized c-FLIP expression by downregulating STAMBPL1, a deubiquitinase (DUB). Specifically, when STAMBPL1 and c-FLIP bound together, STAMBPL1 deubiquitylated c-FLIP. Moreover, STAMBPL1 knockdown markedly increased sensitivity to TRAIL by destabilizing c-FLIP. These findings were further confirmed in vivo using a xenograft model based on the observation that combined treatment with TBMS-1 and TRAIL decreased tumor volume and downregulated STAMBPL1 and c-FLIP expression levels. Overall, our study revealed that STAMBPL1 is essential for c-FLIP stabilization, and that STAMBPL1 depletion enhances TRAIL-mediated apoptosis via c-FLIP downregulation.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
1422-0067
Source
https://www.mdpi.com/1422-0067/24/14/11840
DOI
10.3390/ijms241411840
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/45219
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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