Evidence map›Paper›PMID 31470848›Full record

ArticleJournal of biomedical science2019

Penfluridol triggers cytoprotective autophagy and cellular apoptosis through ROS induction and activation of the PP2A-modulated MAPK pathway in acute myeloid leukemia with different FLT3 statuses.

Szu-Yuan Wu, Yu-Ching Wen, Chia-Chi Ku, Yi-Chieh Yang, Jyh-Ming Chow, Shun-Fa Yang, Wei-Jiunn Lee, Ming-Hsien Chien

Open access · diamondAbstract read
In one paragraph

Article in Journal of biomedical science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
5.4field-weighted citation impact, top 4% of its field
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

19 citing papers in PubMed, 50 citations in OpenAlex.

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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

8 authors at 4 institutions in 1 country.

Szu-Yuan WuDepartment of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Yu-Ching WenDepartment of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Chia-Chi KuGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Yi-Chieh YangGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Jyh-Ming ChowDivision of Hematology and Medical Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Shun-Fa YangInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Wei-Jiunn LeeDepartment of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. lwj5905@gmail.com.
Ming-Hsien ChienGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. mhchien1976@gmail.com.ORCID http://orcid.org/0000-0002-0084-7231
Wan Fang Hospital · TWTaipei Medical University · TWTaipei Medical University Hospital · TWChung Shan Medical University Hospital · TW

Funding

Wan Fang Hospital 108-wf-swf-03
6 · The paper itself

Abstract

backgroundChemotherapy is the main treatment for acute myeloid leukemia (AML), but the cure rates for AML patients remain low, and the notorious adverse effects of chemotherapeutic drugs drastically reduce the life quality of patients. Penfluridol, a long-acting oral antipsychotic drug, has an outstanding safety record and exerts oncostatic effects on various solid tumors. Until now, the effect of penfluridol on AML remains unknown.

methodsAML cell lines harboring wild-type (WT) Fms-like tyrosine kinase 3 (FLT3) and internal tandem duplication (ITD)-mutated FLT3 were used to evaluate the cytotoxic effects of penfluridol by an MTS assay. A flow cytometric analysis and immunofluorescence staining were employed to determine the cell-death phenotype, cell cycle profile, and reactive oxygen species (ROS) and acidic vesicular organelle (AVO) formation. Western blotting and chemical inhibitors were used to explore the underlying mechanisms involved in penfluridol-mediated cell death.

resultsWe observed that penfluridol concentration-dependently suppressed the cell viability of AML cells with FLT3-WT (HL-60 and U937) and FLT3-ITD (MV4-11). We found that penfluridol treatment not only induced apoptosis as evidenced by increases of nuclear fragmentation, the sub-G

conclusionsThese findings provide a rationale for penfluridol being used as a PP2A activator for AML treatment, and the combination of penfluridol with an autophagy inhibitor may be a novel strategy for AML harboring FLT3-WT and FLT3-ITD.

Indexed as

Antipsychotic AgentsApoptosisAutophagyCell Line, TumorCytoprotectionfms-Like Tyrosine Kinase 3HL-60 CellsHumansLeukemia, Myeloid, AcuteMitogen-Activated Protein KinasesPenfluridolProtein Phosphatase 2Reactive Oxygen SpeciesSignal TransductionU937 CellsAntipsychotic Agentsfms-Like Tyrosine Kinase 3Mitogen-Activated Protein KinasesPenfluridolProtein Phosphatase 2Reactive Oxygen SpeciesAcute myeloid leukemiaAktApoptosisAutophagyMitogen-activated protein kinasePenfluridolProtein phosphatase 2 aReactive oxygen species

Identifiers

PMID31470848
PMCPMC6717358
OpenAlexW2970671040

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

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 Socratic graph.