Evidence map›Paper›PMID 32546528›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2020

Voltage-Dependent Anion Channels Influence Cytotoxicity of ME-344, a Therapeutic Isoflavone.

Leilei Zhang, Danyelle M Townsend, Morgan Morris, Eduardo N Maldonado, Yu-Lin Jiang, Ann-Marie Broome, Jennifer R Bethard, Lauren E Ball, Kenneth D Tew

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 39% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. 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

9 authors at 1 institution in 1 country.

Leilei ZhangDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics (L.Z., M.M., E.N.M., Y.-L.J., A.-M.B., J.R.B., L.E.B., K.D.T.) and Department of Pharmaceutical and Biomedical Sciences (D.M.T.), Medical University of South Carolina, Charleston, South Carolina.
Danyelle M TownsendDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics (L.Z., M.M., E.N.M., Y.-L.J., A.-M.B., J.R.B., L.E.B., K.D.T.) and Department of Pharmaceutical and Biomedical Sciences (D.M.T.), Medical University of South Carolina, Charleston, South Carolina.
Morgan MorrisDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics (L.Z., M.M., E.N.M., Y.-L.J., A.-M.B., J.R.B., L.E.B., K.D.T.) and Department of Pharmaceutical and Biomedical Sciences (D.M.T.), Medical University of South Carolina, Charleston, South Carolina.
Eduardo N MaldonadoDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics (L.Z., M.M., E.N.M., Y.-L.J., A.-M.B., J.R.B., L.E.B., K.D.T.) and Department of Pharmaceutical and Biomedical Sciences (D.M.T.), Medical University of South Carolina, Charleston, South Carolina.
Yu-Lin JiangDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics (L.Z., M.M., E.N.M., Y.-L.J., A.-M.B., J.R.B., L.E.B., K.D.T.) and Department of Pharmaceutical and Biomedical Sciences (D.M.T.), Medical University of South Carolina, Charleston, South Carolina.
Ann-Marie BroomeDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics (L.Z., M.M., E.N.M., Y.-L.J., A.-M.B., J.R.B., L.E.B., K.D.T.) and Department of Pharmaceutical and Biomedical Sciences (D.M.T.), Medical University of South Carolina, Charleston, South Carolina.
Jennifer R BethardDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics (L.Z., M.M., E.N.M., Y.-L.J., A.-M.B., J.R.B., L.E.B., K.D.T.) and Department of Pharmaceutical and Biomedical Sciences (D.M.T.), Medical University of South Carolina, Charleston, South Carolina.
Lauren E BallDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics (L.Z., M.M., E.N.M., Y.-L.J., A.-M.B., J.R.B., L.E.B., K.D.T.) and Department of Pharmaceutical and Biomedical Sciences (D.M.T.), Medical University of South Carolina, Charleston, South Carolina.
Kenneth D TewDepartment of Cell and Molecular Pharmacology and Experimental Therapeutics (L.Z., M.M., E.N.M., Y.-L.J., A.-M.B., J.R.B., L.E.B., K.D.T.) and Department of Pharmaceutical and Biomedical Sciences (D.M.T.), Medical University of South Carolina, Charleston, South Carolina tewk@musc.edu.
Medical University of South Carolina · US

Funding

SOUTH CAROLINA COBRE IN OXIDANTS, REDOX BALANCE AND STRESS SIGNALINGP20GM103542 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI WANG, HAIZHEN · 2012 to 2020
$20.2M
Proteomics CoreP30DK123704 · NIDDK · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DON C. ROCKEY · 2020 to 2026
$8.8M
MUSC Minority Student Development ProgramR25GM072643 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ERGUL, ADVIYE, RINKER, JENNIFER ANNE · 2005 to 2023
$5.8M
MUSC Post-Baccalaureate Research Education ProgramR25GM113278 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DELEON-PENNELL, KRISTINE Y, PENROD-MARTIN, RACHEL · 2015 to 2024
$2.7M
MUSC FACIL EXPANSION &RENOV: SLE C06RR015455 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI CROUCH, ROSALIE K · 2002 to 2002
$2.0M
VDAC-Tubulin Regulation of Mitochondrial Membrane Potential HeterogeneityR01CA184456 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MALDONADO, EDUARDO NESTOR · 2016 to 2020
$1.9M
Orbitrap Mass SpectrometerS10OD010731 · OD · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BALL, LAUREN ELIZABETH · 2012 to 2012
$600k
NCI NIH HHS R01 CA184456NCRR NIH HHS C06 RR015455NIDDK NIH HHS P30 DK123704NIGMS NIH HHS P20 GM103542NIGMS NIH HHS R25 GM072643NIGMS NIH HHS R25 GM113278NIH HHS S10 OD010731
6 · The paper itself

Abstract

ME-344 is a second-generation cytotoxic isoflavone with anticancer activity promulgated through interference with mitochondrial functions. Using a click chemistry version of the drug together with affinity-enriched mass spectrometry, voltage-dependent anion channels (VDACs) 1 and 2 were identified as drug targets. To determine the importance of VDAC1 or 2 to cytotoxicity, we used lung cancer cells that were either sensitive (H460) or intrinsically resistant (H596) to the drug. In H460 cells, depletion of VDAC1 and VDAC2 by small interfering RNA impacted ME-344 effects by diminishing generation of reactive oxygen species (ROS), preventing mitochondrial membrane potential dissipation, and moderating ME-344-induced cytotoxicity and mitochondrial-mediated apoptosis. Mechanistically, VDAC1 and VDAC2 knockdown prevented ME-344-induced apoptosis by inhibiting Bax mitochondrial translocation and cytochrome c release as well as apoptosis in these H460 cells. We conclude that VDAC1 and 2, as mediators of the response to oxidative stress, have roles in modulating ROS generation, Bax translocation, and cytochrome c release during mitochondrial-mediated apoptosis caused by ME-344. SIGNIFICANCE STATEMENT: Dissecting preclinical drug mechanisms are of significance in development of a drug toward eventual Food and Drug Administration approval.

Indexed as

Antineoplastic AgentsApoptosisbcl-2-Associated X ProteinCell Line, TumorHumansIsoflavonesMembrane Potential, MitochondrialReactive Oxygen SpeciesVoltage-Dependent Anion Channel 1Voltage-Dependent Anion Channel 2Antineoplastic Agentsbcl-2-Associated X ProteinIsoflavonesME-344Reactive Oxygen SpeciesVoltage-Dependent Anion Channel 1Voltage-Dependent Anion Channel 2

Identifiers

PMID32546528
PMCPMC7372917
OpenAlexW3035139571

What OpenQuestion holds

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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.