Evidence map›Paper›PMID 25640477›Full record

ArticleActa pharmacologica Sinica2015

The antitumor compound triazoloacridinone C-1305 inhibits FLT3 kinase activity and potentiates apoptosis in mutant FLT3-ITD leukemia cells.

Ewa Augustin, Anna Skwarska, Anna Weryszko, Iwona Pelikant, Ewa Sankowska, Barbara Borowa-Mazgaj

Open access · bronzeAbstract readComparative Study
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In one paragraph

Article in Acta pharmacologica Sinica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 38% 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

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 6 citations in OpenAlex.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Ewa AugustinDepartment of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk 80233, Poland.
Anna SkwarskaDepartment of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk 80233, Poland.
Anna WeryszkoDepartment of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk 80233, Poland.
Iwona PelikantDepartment of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk 80233, Poland.
Ewa SankowskaDepartment of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk 80233, Poland.
Barbara Borowa-MazgajDepartment of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk 80233, Poland.
Gdańsk University of Technology · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimFMS-like receptor tyrosine kinase (FLT3) is expressed in some normal hematopoietic cell types and plays an important role in the pathogenesis of acute myeloid leukemia (AML). In this study, we examined the effects of triazoloacridinone C-1305, an antitumor compound, on AML cells with different FLT3 status in vitro.

methodsA panel of human leukemic cell lines with different FLT3 status was used, including FLT3 internal tandem duplication mutations (FLT3-ITD, MV-4-11), wild-type FLT3 (RS-4-11) and null-FLT3 (U937) cells. Cell proliferation was estimated using MTT assays, and apoptosis was studied with flow cytometry and fluorescence microscopy. FLT3 kinase activity (phosphorylation of FLT3 at Tyr591) was determined with ELISA and Western blotting. FLT3 downstream signaling proteins involving AKT, MAPK and STAT5 were examined by Western blotting. RNA silencing was used to decrease the endogenous FLT3.

resultsThe mutant FLT3-ITD cells were more sensitive to C-1305 than the wild-type FLT3 and null-FLT3 cells (the IC50 values measured at 24 h were 1.2±0.17, 2.0±09, 7.6±1.6 μmol/L, respectively). C-1305 (1-10 μmol/L) dose-dependently inhibited the kinase activity of FLT3, which was more pronounced in the mutant FLT3-ITD cells than in the wild-type FLT3 cells. Furthermore, C-1305 dose-dependently decreased the phosphorylation of STAT5 and MAPK and the inhibitory phosphorylation of Bad, and induced time- and dose-dependent apoptosis in the 3 cell lines with the null-FLT3 cells being the least susceptible to C-1305-induced apoptosis. Knockdown of FLT3 with siRNA significantly decreased C-1305-induced cytotoxicity in the mutant FLT3-ITD cells.

conclusionC-1305 induces apoptosis in FLT3-ITD-expressing human leukemia cells in vitro, suggesting that mutated FLT3 kinase can be a new target for C-1305, and C-1305 may be a drug candidate for the therapeutic intervention in FLT3-associated AML.

Indexed as

MutationAcridinesAntineoplastic AgentsApoptosisApoptosis Regulatory ProteinsCell ProliferationDose-Response Relationship, Drugfms-Like Tyrosine Kinase 3HumansLeukemia, Myeloid, AcuteMitogen-Activated Protein KinasesMolecular Targeted TherapyPhosphorylationProtein Kinase InhibitorsProto-Oncogene Proteins c-aktRNA InterferenceAcridinesAntineoplastic AgentsApoptosis Regulatory ProteinsC 1305FLT3 protein, humanfms-Like Tyrosine Kinase 3Mitogen-Activated Protein KinasesProtein Kinase InhibitorsProto-Oncogene Proteins c-aktSTAT5 Transcription FactorTriazoles

Identifiers

PMID25640477
PMCPMC4349925
OpenAlexW2006013432

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