Evidence map›Paper›PMID 26608370›Full record

ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016

MPT0B169, a novel tubulin inhibitor, induces apoptosis in taxol-resistant acute myeloid leukemia cells through mitochondrial dysfunction and Mcl-1 downregulation.

Che-Chuan Wang, Hsinjin Eugene Liu, Yueh-Lun Lee, Yu-Wen Huang, Yi-Ju Chen, Jing-Ping Liou, Huei-Mei Huang

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Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Predicting Chemotherapy Resistance in AML.Current hematologic malignancy reports · 2017
    Review
  3. Article
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

7 authors at 2 institutions in 1 country.

Che-Chuan WangDepartment of Neurosurgery, Chi-Mei Medical Center, No. 901, Zhonghua Rd., Tainan, 710, Taiwan.
Hsinjin Eugene LiuGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, No. 250, Wuxing St., Taipei, 11031, Taiwan.
Yueh-Lun LeeDepartment of Microbiology and Immunology, College of Medicine, Taipei Medical University, No. 250, Wuxing St., Taipei, 11031, Taiwan.
Yu-Wen HuangGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wuxing St., Taipei, 11031, Taiwan.
Yi-Ju ChenGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wuxing St., Taipei, 11031, Taiwan.
Jing-Ping LiouSchool of Pharmacy, College of Pharmacy, Taipei Medical University, No. 250, Wuxing St., Taipei, 11031, Taiwan. jpl@tmu.edu.tw.
Huei-Mei HuangGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wuxing St., Taipei, 11031, Taiwan. cmbhhm@tmu.edu.tw.
Taipei Medical University · TWChi Mei Medical Center · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acute myeloid leukemia (AML) is a hematological malignant disorder. AML cells are not susceptible to chemotherapeutic drugs because of their multidrug resistance (MDR). Antitubulin agents are currently employed in cancer treatments; however, drug resistance results in treatment failures because of MDR1 expressing cancer cells. We previously synthesized a new tubulin inhibitor, 2-dimethylamino-N-[1-(4-methoxy-benzenesulfonyl)-2,3-dihydro-1H-indol-7-yl]-acetamide (MPT0B169), which inhibits AML cell proliferation by arresting cell cycle at the G2/M phase. In this study, we explored the effect of MPT0B169 on apoptosis in AML HL60 and NB4 cells and MDR1-mediated taxol-resistant HL60/TaxR cells and the underlying mechanism. MPT0B169 induced concentration- and time-dependent apoptosis in these cancer cells, as observed through annexin V/propidium iodide double staining and flow cytometry. Furthermore, DNA fragmentation analysis confirmed MPT0B169-induced apoptosis. MPT0B169 induced a loss of mitochondrial membrane potential, release of cytochrome c into the cytosol, cleavage and activation of caspase-9 and caspase-3, and consequently cleavage of poly (ADP ribose) polymerase. Western blot analysis showed that MPT0B169 markedly reduced Mcl-1 (an antiapoptotic protein) levels; however, it caused no changes in Bcl-2 or BAX (a proapoptotic protein). Knockdown of Mcl-1 using small interfering RNA (siRNA) slightly induced growth inhibition and apoptosis in the HL60 and HL60/TaxR cells. Further investigation revealed that Mcl-1 siRNA enhanced the sensitivity of HL60 and HL60/TaxR cells to MPT0B169-induced growth inhibition and apoptosis. Together, these results demonstrated that MPT0B169-induced apoptosis in nonresistant and MDR1-mediated taxol-resistant AML cells through Mcl-1 downregulation and a mitochondria-mediated pathway. MPT0B169 can overcome MDR1-mediated drug resistance in AML cells.

Indexed as

Drug Resistance, NeoplasmApoptosisCaspase 3Caspase 9Cell Line, TumorCytochromes cGene Expression Regulation, LeukemicGene Knockdown TechniquesHL-60 CellsHumansLeukemia, Myeloid, AcuteMembrane Potential, MitochondrialMitochondriaMyeloid Cell Leukemia Sequence 1 ProteinPaclitaxelSarcosine2-dimethylamino-N-(1-(4-methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-7-yl)acetamideCaspase 3Caspase 9Cytochromes cMyeloid Cell Leukemia Sequence 1 ProteinPaclitaxelSarcosineSulfonamidesTubulin ModulatorsAcute myeloid leukemia cellsMcl-1MDR1-mediated resistanceMitochondria-mediated apoptosisMPT0B169Tubulin inhibitor

Identifiers

PMID26608370
OpenAlexW2179360812

What OpenQuestion holds

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Read underepoch 390

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.