Evidence map›Paper›PMID 30612055›Full record

ArticleLeukemia research2019

Tropolone-induced effects on the unfolded protein response pathway and apoptosis in multiple myeloma cells are dependent on iron.

Staci L Haney, Michelle L Varney, Hannah R Safranek, Yashpal S Chhonker, Narendran G-Dayanandan, Geoffrey Talmon, Daryl J Murry, Andrew J Wiemer, Dennis L Wright, Sarah A Holstein

Open access · greenAbstract read
In one paragraph

Article in Leukemia research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Perls' Prussian Blue Stains of Lung Tissue, Bronchoalveolar Lavage, and Sputum.Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer · 2021
    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

10 authors at 3 institutions in 1 country.

Staci L HaneyDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States.
Michelle L VarneyDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States.
Hannah R SafranekDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States.
Yashpal S ChhonkerDepartment of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE, United States.
Narendran G-DayanandanDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, United States.
Geoffrey TalmonDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United States.
Daryl J MurryDepartment of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE, United States.
Andrew J WiemerDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, United States.
Dennis L WrightDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, United States.
Sarah A HolsteinDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States. Electronic address: sarah.holstein@unmc.edu.
University of Nebraska Medical Center · USUniversity of Connecticut · USNebraska Medical Center · US

Funding

UNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI James Eudy · 1985 to 2026
$55.0M
UNMC Summer Undergraduate Alcohol Research ProgramR25AA020818 · NIAAA · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Kristina L Bailey · 2012 to 2026
$931k
HDAC Inhibitors Inspired by Natural ProductsR21CA162470 · NCI · UNIVERSITY OF CONNECTICUT STORRS · PI WRIGHT, DENNIS L. · 2011 to 2012
$361k
NCI NIH HHS P30 CA036727NCI NIH HHS R21 CA162470NIAAA NIH HHS R25 AA020818
6 · The paper itself

Abstract

Tropolones are naturally occurring seven-membered non-benzenoid aromatic compounds that are of interest due to their cytotoxic properties. MO-OH-Nap is a novel α-substituted tropolone that induces caspase cleavage and upregulates markers associated with the unfolded protein response (UPR) in multiple myeloma (MM) cells. Given previous reports that tropolones may function as iron chelators, we investigated the effects of MO-OH-Nap, as well as the known iron chelator deferoxamine (DFO), in MM cells in the presence or absence of supplemental iron. The ability of MO-OH-Nap to induce apoptosis and upregulate markers of the UPR could be completely prevented by co-incubation with either ferric chloride or ammonium ferrous sulfate. Iron also completely prevented the decrease in BrdU incorporation induced by either DFO or MO-OH-Nap. Ferrozine assays demonstrated that MO-OH-Nap directly chelates iron. Furthermore, MO-OH-Nap upregulates cell surface expression and mRNA levels of transferrin receptor. In vivo studies demonstrate increased Prussian blue staining in hepatosplenic macrophages in MO-OH-Nap-treated mice. These studies demonstrate that MO-OH-Nap-induced cytotoxic effects in MM cells are dependent on the tropolone's ability to alter cellular iron availability and establish new connections between iron homeostasis and the UPR in MM.

Indexed as

AnimalsApoptosisCell CycleCell ProliferationChloridesDeferoxamineFemaleFerric CompoundsFerrous CompoundsHumansIronIron Chelating AgentsMiceMultiple MyelomaQuaternary Ammonium CompoundsReceptors, Transferrinammonium ferrous sulfateChloridesDeferoxamineferric chlorideFerric CompoundsFerrous CompoundsIronIron Chelating AgentsQuaternary Ammonium CompoundsReceptors, TransferrinSiderophoresTropoloneApoptosisIronMultiple myelomaTropoloneUnfolded protein response pathway

Identifiers

PMID30612055
PMCPMC6456044
OpenAlexW2905948204

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.