Evidence map›Paper›PMID 33276759›Full record

ArticleBMC cancer2020

Radotinib enhances cytarabine (Ara-C)-induced acute myeloid leukemia cell death.

Sook-Kyoung Heo, Eui-Kyu Noh, Ho-Min Yu, Do Kyoung Kim, Hye Jin Seo, Yoo Jin Lee, Jaekyung Cheon, Su Jin Koh, Young Joo Min, Yunsuk Choi and 1 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

7 citing papers in PubMed, 12 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

11 authors at 1 institution in 1 country.

Sook-Kyoung HeoBiomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 44033, Republic of Korea.
Eui-Kyu NohDepartment of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwan-doro, Dong-gu, Ulsan, 44033, Republic of Korea.
Ho-Min YuBiomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 44033, Republic of Korea.
Do Kyoung KimBiomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 44033, Republic of Korea.
Hye Jin SeoBiomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 44033, Republic of Korea.
Yoo Jin LeeDepartment of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwan-doro, Dong-gu, Ulsan, 44033, Republic of Korea.
Jaekyung CheonDepartment of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwan-doro, Dong-gu, Ulsan, 44033, Republic of Korea.
Su Jin KohDepartment of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwan-doro, Dong-gu, Ulsan, 44033, Republic of Korea.
Young Joo MinDepartment of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwan-doro, Dong-gu, Ulsan, 44033, Republic of Korea.
Yunsuk ChoiDepartment of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwan-doro, Dong-gu, Ulsan, 44033, Republic of Korea. choiysmd@gmail.com.
Jae-Cheol JoBiomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 44033, Republic of Korea. jcjo97@hanmail.net.ORCID http://orcid.org/0000-0001-6014-7977
Ulsan College · KR

Funding

National Research Foundation of Korea 2017R1A1A3A04069314Ulsan University Hospital UUH-2019-06Ulsan University Hospital UUHBRC-2016-001
6 · The paper itself

Abstract

backgroundAcute myeloid leukemia (AML) is a heterogeneous disease that frequently relapses after standard chemotherapy. Therefore, there is a need for the development of novel chemotherapeutic agents that could treat AML effectively. Radotinib, an oral BCR-ABL tyrosine kinase inhibitor, was developed as a drug for the treatment of chronic myeloid leukemia. Previously, we reported that radotinib exerts increased cytotoxic effects towards AML cells. However, little is known about the effects of combining radotinib with Ara-C, a conventional chemotherapeutic agent for AML, with respect to cell death in AML cells. Therefore, we investigated combination effects of radotinib and Ara-C on AML in this study.

methodsSynergistic anti-cancer effects of radotinib and Ara-C in AML cells including HL60, HEL92.1.7, THP-1 and bone marrow cells from AML patients have been examined. Diverse cell biological assays such as cell viability assay, Annexin V-positive cells, caspase-3 activity, cell cycle distribution, and related signaling pathway have been performed.

resultsThe combination of radotinib and Ara-C was found to induce AML cell apoptosis, which involved the mitochondrial pathway. In brief, combined radotinib and Ara-C significantly induced Annexin V-positive cells, cytosolic cytochrome C, and the pro-apoptotic protein Bax in AML cells including HL60, HEL92.1.7, and THP-1. In addition, mitochondrial membrane potential and Bcl-xl protein were markedly decreased by radotinib and Ara-C. Moreover, this combination induced caspase-3 activity. Cleaved caspase-3, 7, and 9 levels were also increased by combined radotinib and Ara-C. Additionally, radotinib and Ara-C co-treatment induced G

conclusionsTherefore, our results can be concluded that radotinib in combination with Ara-C possesses a strong anti-AML activity.

Indexed as

AnimalsAntimetabolites, AntineoplasticAntineoplastic AgentsApoptosisBenzamidesCell CycleCytarabineDaunorubicinDrug SynergismHL-60 CellsHumansIdarubicinLeukemia, Myeloid, AcuteMaleMembrane Potential, MitochondrialMice4-methyl-N-(3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl)-3-(4-pyrazin-2-ylpyrimidin-2-ylamino)benzamideAntimetabolites, AntineoplasticAntineoplastic AgentsBenzamidesCytarabineDaunorubicinIdarubicinNeoplasm ProteinsProtein Kinase InhibitorsPyrazinesAcute myeloid leukemiaAnti-leukemic activityAra-CCytarabineRadotinib

Identifiers

PMID33276759
PMCPMC7718665
OpenAlexW3107427950

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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.