ArticleBlood2006
The tyrphostin adaphostin interacts synergistically with proteasome inhibitors to induce apoptosis in human leukemia cells through a reactive oxygen species (ROS)-dependent mechanism.
Article in Blood, 2006. 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 It has been retracted, and should not be counted.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 15 papers.
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.
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.
Who cites it
15 citing papers in PubMed, 94 citations in OpenAlex.
- Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines.Cancer investigation · 2011Trial
- Anti-dsDNA antibodies bind to TLR4 and activate NLRP3 inflammasome in lupus monocytes/macrophages.Journal of translational medicine · 2016Article
- The lipophilic bullet hits the targets: medicinal chemistry of adamantane derivatives.Chemical reviews · 2013Review
- Effects of antioxidants and MAPK inhibitors on cell death and reactive oxygen species levels in HOncology letters · 2013Article
- Redox control of leukemia: from molecular mechanisms to therapeutic opportunities.Antioxidants & redox signaling · 2013Review
- MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion.Oncology reports · 2012Article
- Article
- The ubiquitin/26S proteasome system in plant-pathogen interactions: a never-ending hide-and-seek game.Molecular plant pathology · 2010Review
- Bcl-2 antagonists interact synergistically with bortezomib in DLBCL cells in association with JNK activation and induction of ER stress.Cancer biology & therapy · 2009Article
- Oxidative stress by targeted agents promotes cytotoxicity in hematologic malignancies.Antioxidants & redox signaling · 2009Review
- c-Jun N-terminal kinase activation failure is a new mechanism of anthracycline resistance in acute myeloid leukemia.Leukemia · 2008Article
- Article
- Article
- The role of the NADPH oxidase complex, p38 MAPK, and Akt in regulating human monocyte/macrophage survival.American journal of respiratory cell and molecular biology · 2007Article
- Adaphostin has significant and selective activity against chronic and acute myeloid leukemia cells.Cancer science · 2006Article
Corrections and comments
- Retraction · 2019-05-24Duplication of/in Image · Falsification/Fabrication of Data · Investigation by Company/Institution · Investigation by ORI · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · · Girija Dasmahapatra has an ORI finding of misconduct;
- Commented on by
- Commented on by
- Retracted
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Interactions between the tyrphostin adaphostin and proteasome inhibitors (eg, MG-132 and bortezomib) were examined in multiple human leukemia cell lines and primary acute myeloid leukemia (AML) specimens. Cotreatment of Jurkat cells with marginally toxic concentrations of adaphostin and proteasome inhibitors synergistically potentiated mitochondrial damage (eg, cytochrome c release), caspase activation, and apoptosis. Similar interactions occurred in other human leukemia cell types (eg, U937, HL-60, Raji). These interactions were associated with a marked increase in oxidative damage (eg, ROS generation), down-regulation of the Raf/MEK/ERK pathway, and JNK activation. Adaphostin/MG-132 lethality as well as mitochondrial damage, down-regulation of Raf/MEK/ERK, and activation of JNK were attenuated by the free-radical scavenger NAC, suggesting that oxidative damage plays a functional role in antileukemic effects. Ectopic expression of Raf-1 or constitutively active MEK/ERK or genetic interruption of the JNK pathway significantly diminished adaphostin/MG-132-mediated lethality. Interestingly, enforced Raf or MEK/ERK activation partially diminished adaphostin/MG-132-mediated ROS generation, suggesting the existence of an amplification loop. Finally, the adaphostin/MG-132 regimen displayed similar toxicity toward 5 primary AML samples but not normal hematopoietic progenitors (eg, bone marrow CD34+ cells). Collectively, these findings suggest that potentiating oxidative damage by combining adaphostin with proteasome inhibitors warrants attention as an antileukemic strategy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.