Evidence map›Paper›PMID 34958363›Full record

ArticleMetallomics : integrated biometal science2022

The ionophore thiomaltol induces rapid lysosomal accumulation of copper and apoptosis in melanoma.

Ottis Scrivner, Long Dao, M Karen Newell-Rogers, Babbak Shahandeh, Frank L Meyskens, Susan Kurumi Kozawa, Feng Liu-Smith, Germán Plascencia-Villa, Miguel José-Yacamán, Shang Jia and 2 more

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

Article in Metallomics : integrated biometal science, 2022. 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
0.2field-weighted citation impact, top 46% 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, 7 citations in OpenAlex.

  1. Article
  2. Metal Ion Signaling in Biomedicine.Chemical reviews · 2025
    Review
  3. Cuproptosis: Mechanism and Application in Lymphoma.Current cancer drug targets · 2025
    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

12 authors at 7 institutions in 1 country.

Ottis ScrivnerDepartment of Chemistry & Biochemistry, Baylor University, Waco, TX 76706, USA.ORCID 0000-0002-1358-8902
Long DaoDepartment of Medical Physiology, College of Medicine, Texas A&M Health Sciences Center, Bryan, TX 77807, USA.
M Karen Newell-RogersDepartment of Medical Physiology, College of Medicine, Texas A&M Health Sciences Center, Bryan, TX 77807, USA.
Babbak ShahandehDepartment of Medicine, UC Irvine, Irvine, CA 92617, USA.
Frank L MeyskensDepartment of Medicine, UC Irvine, Irvine, CA 92617, USA.
Susan Kurumi KozawaDepartment of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Feng Liu-SmithDepartment of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Germán Plascencia-VillaDepartment of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX 78249, USA.
Miguel José-YacamánApplied Physics and Materials Science Department and MIRA Center, Northern Arizona University, Flagstaff, AZ 86011, USA.
Shang JiaDepartment of Chemistry, University of California, Berkeley, CA 94720, USA.
Christopher J ChangDepartment of Chemistry, University of California, Berkeley, CA 94720, USA.
Patrick J FarmerDepartment of Chemistry & Biochemistry, Baylor University, Waco, TX 76706, USA.ORCID 0000-0001-9911-999X
Baylor University · USTexas A&M Health Science Center · USUniversity of California, Berkeley · USUniversity of California, Irvine · USUniversity of Tennessee Health Science Center · USNorthern Arizona University · USThe University of Texas at San Antonio · US

Funding

Molecular Imaging Probes To Study Redox BiologyR01GM079465 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Christopher J. Chang · 2006 to 2026
$7.8M
NIGMS NIH HHS R01 GM079465
6 · The paper itself

Abstract

In this report, we investigate the toxicity of the ionophore thiomaltol (Htma) and Cu salts to melanoma. Divalent metal complexes of thiomaltol display toxicity against A375 melanoma cell culture resulting in a distinct apoptotic response at submicromolar concentrations, with toxicity of Cu(tma)2 > Zn(tma)2 >> Ni(tma)2. In metal-chelated media, Htma treatment shows little toxicity, but the combination with supplemental CuCl2, termed Cu/Htma treatment, results in toxicity that increases with suprastoichiometric concentrations of CuCl2 and correlates with the accumulation of intracellular copper. Electron microscopy and confocal laser scanning microscopy of Cu/Htma treated cells shows a rapid accumulation of copper within lysosomes over the course of hours, concurrent with the onset of apoptosis. A buildup of ubiquitinated proteins due to proteasome inhibition is seen on the same timescale and correlates with increases of copper without additional Htma.

Indexed as

CopperMelanomaApoptosisHumansIonophoresLysosomesPyransThiones3-hydroxy-2-methyl-4H-pyran-4-thioneCopperIonophoresPyransThionesapoptosiscopper ionophoremelanomaproteasome inhibitionthiomaltol

Identifiers

PMID34958363
PMCPMC8763036
OpenAlexW4200098710

What OpenQuestion holds

Textmetadata
Read underepoch 390

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 OpenQuestion graph.