Evidence map›Paper›PMID 39286953›Full record

ArticleCancer biology & therapy2024

EX527, a sirtuins 1 inhibitor, sensitizes T-cell leukemia to death receptor-mediated apoptosis by downregulating cellular FLICE inhibitory protein.

Rongqi Guo, Yihui Wei, Yating Du, Luyue Liu, Haoqi Zhang, Ruiying Ren, Ruili Sun, Tingting Zhang, Xiwen Xiong, Lijun Zhao and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer biology & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Rongqi GuoDepartment of Clinical Laboratory, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
Yihui WeiHenan Red Cross Blood Center, Xinxiang, China.
Yating DuDepartment of Clinical Laboratory, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
Luyue LiuDepartments of Laboratory Medicine, Zhoukou Central Hospital, Zhoukou, China.
Haoqi ZhangDepartment of Microbiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
Ruiying RenDepartment of Clinical Laboratory, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
Ruili SunHenan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
Tingting ZhangDepartment of Microbiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
Xiwen XiongSchool of Forensic Medicine, Xinxiang Medical University, Xinxiang, China.
Lijun ZhaoHenan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
Hongfei WangHenan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
Xiaofang GuoXinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, Xinxiang Medical University, Xinxiang, China.
Xiaofei ZhuDepartment of Clinical Laboratory, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.ORCID 0000-0001-6360-140X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Death receptor-mediated extrinsic apoptosis system had been developed as a promising therapeutic strategy in clinical oncology, such as TRAIL therapy. However, multiple studies have demonstrated that TRAIL resistance is the biggest problem for disappointing clinical trials despite preclinical success. Targeting cellular FLICE inhibitory protein (cFLIP) is one strategy of combinatorial therapies to overcome resistance to DR-mediated apoptosis due to its negative regulator of extrinsic apoptosis. E × 527 (Selisistat) is a specific inhibitor of SIRT1 activity with safe and well tolerance in clinical trials. Here, we show that E × 527 could strengthen significantly activation of rhFasL-mediated apoptotic signaling pathway and increased apoptotic rate of T leukemia cells with high expression of cFLIP. Mechanically, Inhibition of SIRT1 by E × 527 increased polyubiquitination level of cFLIP via increasing acetylation of Ku70, which could promote proteosomal degradation of cFLIP protein. It implied that combinatorial therapies of E × 527 plus TRAIL may have a potential as a novel clinical application for TRAIL-resistant hematologic malignancies.

Indexed as

ApoptosisCASP8 and FADD-Like Apoptosis Regulating ProteinSirtuin 1TNF-Related Apoptosis-Inducing LigandAnimalsAzocinesBenzhydryl CompoundsCarbazolesCell Line, TumorDown-RegulationHumansKu AutoantigenLeukemia, T-CellMiceSignal TransductionAzocinesBenzhydryl CompoundsCarbazolesCASP8 and FADD-Like Apoptosis Regulating ProteinCFLAR protein, humanKu AutoantigenN-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamideSIRT1 protein, humanSirtuin 1TNF-Related Apoptosis-Inducing Ligandapoptosiscellular flice-inhibitory proteinEX527sirtuins 1T leukemia

Identifiers

PMID39286953
PMCPMC11409494

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.