Evidence map›Paper›PMID 25239935›Full record

ArticleMolecular cancer therapeutics2014

In vitro and in vivo interactions between the HDAC6 inhibitor ricolinostat (ACY1215) and the irreversible proteasome inhibitor carfilzomib in non-Hodgkin lymphoma cells.

Girija Dasmahapatra, Hiral Patel, Johnathan Friedberg, Steven N Quayle, Simon S Jones, Steven Grant

RetractedOpen access · bronzeAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

22 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Recent Update of HDAC Inhibitors in Lymphoma.Frontiers in cell and developmental biology · 2020
    Review
  5. Retraction:Molecular cancer therapeutics · 2019
    Article
  6. Histone deacetylase 6 in cancer.Journal of hematology & oncology · 2018
    Review
  7. The Therapeutic Strategy of HDAC6 Inhibitors in Lymphoproliferative Disease.International journal of molecular sciences · 2018
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Changes in cardiac Nav1.5 expression, function, and acetylation by pan-histone deacetylase inhibitors.American journal of physiology. Heart and circulatory physiology · 2016
    Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Girija DasmahapatraDivision of Hematology/Oncology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia.
Hiral PatelDivision of Hematology/Oncology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia.
Johnathan FriedbergJames T. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York. Department of Medicine, University of Rochester Medical Center, Rochester, New York. Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York.
Steven N QuayleAcetylon Pharmaceuticals Inc., Boston, Massachusetts.
Simon S JonesAcetylon Pharmaceuticals Inc., Boston, Massachusetts.
Steven GrantDivision of Hematology/Oncology, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia. Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia. Virginia Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, Virginia. stgrant@vcu.edu.
Virginia Commonwealth University · USAcetylon Pharmaceuticals (United States) · USUniversity of Rochester Medical Center · US

Funding

SPORE in LymphomaP50CA130805 · NCI · UNIVERSITY OF ROCHESTER · PI FISHER, RICHARD I · 2008 to 2012
$11.7M
P4 -TARGETING MULTIPLE MYELOMA BY COMBINING CDK INHIBITORS AND BCL-2 ANTAGONISTSP50CA142509 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KWAK, LARRY W · 2010 to 2014
$11.1M
NF-kappaB Inhibitors and Differentiation-Inducers in LeukemiaR01CA093738 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI GRANT, STEVEN · 2002 to 2011
$2.4M
Checkpoint Abrogation and MEK 1/2 Inhibition in MyelomaR01CA100866 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI GRANT, STEVEN · 2003 to 2013
$2.2M
Promotion of Nucleoside Analog Induced Apoptosis by HDIsR01CA063753 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI GRANT, STEVEN · 1994 to 2008
$2.2M
NCI NIH HHS 1P50 CA130805NCI NIH HHS CA100866NCI NIH HHS CA63753NCI NIH HHS CA93738NCI NIH HHS P50 CA130805NCI NIH HHS P50 CA142509NCI NIH HHS P50CA142509NCI NIH HHS R01 CA063753NCI NIH HHS R01 CA093738NCI NIH HHS R01 CA100866
6 · The paper itself

Abstract

Interactions between the HDAC6 inhibitor ricolinostat (ACY1215) and the irreversible proteasome inhibitor carfilzomib were examined in non-Hodgkin lymphoma (NHL) models, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and double-hit lymphoma cells. Marked in vitro synergism was observed in multiple cell types associated with activation of cellular stress pathways (e.g., JNK1/2, ERK1/2, and p38) accompanied by increases in DNA damage (γH2A.X), G2-M arrest, and the pronounced induction of mitochondrial injury and apoptosis. Combination treatment with carfilzomib and ricolinostat increased reactive oxygen species (ROS), whereas the antioxidant TBAP attenuated DNA damage, JNK activation, and cell death. Similar interactions occurred in bortezomib-resistant and double-hit DLBCL, MCL, and primary DLBCL cells, but not in normal CD34(+) cells. However, ricolinostat did not potentiate inhibition of chymotryptic activity by carfilzomib. shRNA knockdown of JNK1 (but not MEK1/2), or pharmacologic inhibition of p38, significantly reduced carfilzomib-ricolinostat lethality, indicating a functional contribution of these stress pathways to apoptosis. Combined exposure to carfilzomib and ricolinostat also markedly downregulated the cargo-loading protein HR23B. Moreover, HR23B knockdown significantly increased carfilzomib- and ricolinostat-mediated lethality, suggesting a role for this event in cell death. Finally, combined in vivo treatment with carfilzomib and ricolinostat was well tolerated and significantly suppressed tumor growth and increased survival in an MCL xenograft model. Collectively, these findings indicate that carfilzomib and ricolinostat interact synergistically in NHL cells through multiple stress-related mechanisms, and suggest that this strategy warrants further consideration in NHL.

Indexed as

AnimalsApoptosisCell Cycle CheckpointsCell Line, TumorDisease Models, AnimalDNA-Binding ProteinsDNA Repair EnzymesDrug InteractionsDrug SynergismFemaleGene Knockdown TechniquesHistone Deacetylase 6Histone Deacetylase InhibitorsHistone DeacetylasesHumansHydroxamic AcidscarfilzomibDNA-Binding ProteinsDNA Repair EnzymesHDAC6 protein, humanHistone Deacetylase 6Histone Deacetylase InhibitorsHistone DeacetylasesHydroxamic AcidsOligopeptidesProteasome InhibitorsPyrimidinesRAD23B protein, humanReactive Oxygen SpeciesricolinostatRNA, Small Interfering

Identifiers

PMID25239935
PMCPMC4304772
OpenAlexW2133590787

What OpenQuestion 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 OpenQuestion graph.