Evidence map›Paper›PMID 23656719›Full record

ArticleMolecular cancer2013

6-Formylindolo (3,2-b)carbazole (FICZ) enhances retinoic acid (RA)-induced differentiation of HL-60 myeloblastic leukemia cells.

Rodica P Bunaciu, Andrew Yen

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

20 citing papers in PubMed, 31 citations in OpenAlex.

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  14. New Trends in Aryl Hydrocarbon Receptor Biology.Frontiers in cell and developmental biology · 2016
    Review
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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

2 authors at 1 institution in 1 country.

Rodica P BunaciuDepartment of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
Andrew Yen
Cornell University · US

Funding

TRANS-NETWORK PROJECTSU54CA143876 · NCI · CORNELL UNIVERSITY · PI SHULER, MICHAEL L · 2009 to 2014
$12.6M
NUTRITIONAL CELL CYCLE AND DIFFERENTIATION CONTROLR01CA033505 · NCI · UNIVERSITY OF IOWA · PI YEN, ANDREW · 1985 to 2013
$3.2M
Mechanism of Action of Retinoic Acid Using CD38R01CA152870 · NCI · CORNELL UNIVERSITY · PI HAO, QUAN, LIN, HENING · 2011 to 2015
$1.6M
NCI NIH HHS R01 CA033505NCI NIH HHS R01 CA152870NCI NIH HHS U54 CA143876
6 · The paper itself

Abstract

backgroundThe aryl hydrocarbon receptor (AhR) ligand 6-Formylindolo(3,2-b)carbazole (FICZ) has received increasing attention since its identification as an endogenous AhR ligand and a photoproduct of tryptophan. FICZ and its metabolites have been detected in human fluids. We recently reported that AhR promotes retinoic acid (RA)-induced granulocytic differentiation of HL-60 myeloblastic leukemia cells by restricting the nuclear abundance of the stem cell associated transcription factor Oct4. The standard clinical management of acute promyelocytic leukemia (APL) is differentiation induction therapy using RA. But RA is not effective for other myeloid leukemias, making the mechanism of RA-induced differentiation observed in a non-APL myeloid leukemia of interest. To our knowledge, this is the first study regarding the influence of FICZ on RA-induced differentiation in any type of leukemic blasts.

methodsUsing flow cytometry and Western blotting assays, we determined the effects of FICZ on RA-induced differentiation of HL-60 human leukemia cells. All experiments were performed in triplicate. The groups RA and FICZ + RA were compared using the Paired-Samples T-Test. Western blot figures present the typical blots.

resultsWe demonstrate that FICZ enhances RA-induced differentiation, assessed by the expression of the membrane differentiation marker CD11b; cell cycle arrest; and the functional differentiation marker, inducible-oxidative metabolism. FICZ causes changes in signaling events that are known to drive differentiation, and notably augments the RA-induced sustained activation of the RAF/MEK/ERK axis of the mitogen-activated protein kinase (MAPK) cascade. FICZ also augments expression of the known MAPK signaling regulatory molecules c-Cbl, VAV1, pY458 p85 PI3K, Src-family kinases (SFKs), and IRF-1, a transcription factor associated with this putative signalsome that promotes RA-induced differentiation. Moreover, FICZ in combination with RA also increases expression of AhR and even more so of both Cyp1A2 and p47phox, which are known to be transcriptionally regulated by AhR. pY1021 PDGFRβ, a marker associated with retinoic acid syndrome was also increased.

conclusionsOur data suggest that FICZ modulates intracellular signaling pathways and enhances RA-induced differentiation.

Indexed as

CarbazolesCell CycleCell DifferentiationDrug SynergismGene Expression Regulation, LeukemicHL-60 CellsHumansLeukemia, Promyelocytic, AcuteLigandsMitogen-Activated Protein KinasesModels, BiologicalPhosphorylationProto-Oncogene Proteins c-rafReceptors, Aryl HydrocarbonSignal TransductionTretinoin6-formylindolo(3,2-b)carbazoleCarbazolesLigandsMitogen-Activated Protein KinasesProto-Oncogene Proteins c-rafReceptors, Aryl HydrocarbonTretinoin

Identifiers

PMID23656719
PMCPMC3693992
OpenAlexW2097298305

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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.