scholarly journals 3’, 4’-Dihydroxyflavone enhances all-trans retinoic acid-induced superoxide-generating activity through up-regulating transcription of gp91-phox in human monoblastic U937 cells, as opposed to flavone and other hydroxyflavone derivatives

2021 ◽  
Vol 8 (2) ◽  
pp. 53-59
Author(s):  
Hidehiko Kikuchi ◽  
Kaori Harata ◽  
Sumiko Akiyoshi ◽  
Harishkumar Madhyastha ◽  
Futoshi Kuribayashi
Keyword(s):  
Retinoic Acid ◽  
U937 Cells

scholarly journals Sulforaphane displays the growth inhibition, cytotoxicity and enhancement of retinoic acid-induced superoxide-generating activity in human monoblastic U937 cells

2019 ◽  
Vol 6 (8) ◽  
pp. 319-325 ◽  
Author(s):  
Sumiko Akiyoshi ◽  
Hidehiko Kikuchi ◽  
Futoshi Kuribayashi ◽  
Harishkumar Madhyastha ◽  
Hisanori Minami
Keyword(s):  
Retinoic Acid ◽  
Growth Inhibition ◽  
U937 Cells

scholarly journals Cooperative Effects of a Dnmt Inhibitor and All-Trans Retinoic Acid in an AML Cell Line Model Lacking PML-Rara

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1359-1359
Author(s):  
Ruth Meier ◽  
Gabriele Greve ◽  
Christoph Niemöller ◽  
Heiko Becker ◽  
Tobias Ma ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Colony Formation ◽  
Study Drug ◽  
Interferon Response ◽  
Cdna Libraries ◽  
U937 Cells ◽  
Go Analysis ◽  
Retinoic Acid Response Element ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Introduction: All-trans retinoic acid (ATRA, RA) has powerful activity in acute promyelocytic leukemia (APL); its efficacy in non-APL acute myeloid leukemia (AML) is still unclear, but may be enhanced by epigenetic drugs such as azanucleoside DNMT inhibitors (Blagitko-Dorfs et al. PLoS ONE 2013). In a randomized phase II study (DECIDER trial, NCT00867672) the addition of RA to decitabine (DAC) in newly diagnosed non-fit older AML patients resulted in a clinically meaningful extension of survival. We hypothesize that the add-on of RA to DAC results in cooperative transcriptome changes (possibly associated with demethylation) which may, at least in part, explain these clinical results. Materials and Methods: U937 cells were treated in triplicates with daily pulses of 200 nM DAC, 1 µM RA was administered after 48 hours (hr). Cells were harvested after 72 and 120 hr of treatment. Proliferation and apoptosis were determined by acridine orange / propidium iodide staining. For the colony formation assay (CFA), 100 cells were seeded after 120 hr treatment in methylcellulose, colonies were counted after 21 days. Stranded cDNA libraries were sequenced on an Illumina HiSeq2000 with 60 million 125 bp paired-end reads. Read quality was checked with FastQC (per base Q-score >38), alignment to the GencodeCompV24 reference genome with RNAStar, generation of count matrices with ht-seq and differential expression testing with DeSeq2. Transcript changes were considered significant with an adjusted FDR p-value < 0.01. GO analysis was performed with Metascape. Methylomes were generated using Infinium Human Methylation 450K BeadChip arrays and differential methylation data was obtained using the RnBeads package for R (Assenov et al. Nature Methods 2014). Results: In suspension culture, RA alone had no effect on the proliferation of U937 cells, DAC alone reduced proliferation by 74 %, the DAC+RA combination by 81 % (with viability always ≥ 90 %). RA alone also had no effect on colony growth, DAC reduced colony formation by 85 %, and DAC+RA decreased colony numbers by 96 %. To determine transcriptional add-on effects of DAC+RA, transcriptomes of cells treated for 72 hr were analyzed by RNA-Seq. RA alone had a modest effect on transcription, whereas DAC alone induced / downregulated 2538 and 620 transcripts, DAC+RA induced / downregulated 2848 and 1173 transcripts, respectively (Table 1, Fig. 1). 29.6 % (1192 transcripts) of all DAC+RA-altered transcripts were uniquely regulated by the combination and not by DAC or RA alone. GO analysis of the DAC+ATRA alone upregulated genes (664 transcripts) revealed a significant enrichment for immune system and cellular decay terms, downregulated genes were enriched for transcription and cell cycle terms. Of the transcripts already up- or downregulated by DAC or RA alone, 55.5 % of were further enhanced by DAC+RA. Among those, the retinoic acid receptors RARA, RARB and the retinoic acid response element (RARE)-containing tumor suppressor HIC-1 (Hassan et al. Cell Reports 2017) were induced 8.6-, 8.3- and 179.8-fold, respectively, compared to 2.4- and 5.3-fold (RARA and RARB, DAC alone) and 26.5-fold (HIC-1, RA alone) (validated by qRT-PCR). Among the most regulated uniquely induced transcripts by DAC+RA, the RA-regulating cytochrome P450 member CYP26A1 (regulated by multiple RAREs) was upregulated 347.3-fold. In order to further investigate this add-on effect of RA on DAC-induced transcriptome changes, DNA methylation was analyzed (72 and 120 hr). As expected, DAC significantly reduced CpG methylation in gene bodies and promoters, without further demethylation upon RA add-on after 72 hr (after 120 hr, a trend towards further demethylation was noted with DAC+ATRA). Conclusion: In vitro, the combination of DAC with RA resulted in enhanced growth inhibition and reduced colony formation compared to DAC alone. Transcriptome analysis revealed a high number of uniquely regulated transcripts, and an enhancement of regulation by the combination treatment. As expected, this also included genes with RAREs. The enrichment for genes involved in immune response (e.g. multiple interferon-response genes) encourages the combination of DNMTi-based therapies with immunotherapeutic agents. Therefore, further transcriptome analyses of transposable elements, when reactivated, may trigger an interferon-mediated immune reaction, are currently ongoing. Disclosures Lübbert: TEVA: Other: Study drug; Celgene: Other: Travel Support; Cheplapharm: Other: Study drug; Janssen: Honoraria, Research Funding.

scholarly journals Proteasome (Prosome) Subunit Variations during the Differentiation of Myeloid U937 Cells

1997 ◽  
Vol 15 (3) ◽  
pp. 131-144 ◽  
Author(s):  
Laurent Henry ◽  
Ahsene Baz ◽  
Marie-Thérèse Château ◽  
René Caravano ◽  
Klaus Scherrer ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Retinoic Acid ◽  
Western Blot ◽  
Control Level ◽  
U937 Cells ◽  
Myristate Acetate ◽  
Multicatalytic Proteinase ◽  
Undifferentiated Cells ◽  
Proteasome Subunits ◽  
Protein Particles

20S proteasomes (prosomes/multicatalytic proteinase) are protein particles built of 28 subunits in variable composition. We studied the changes in proteasome subunit composition during the differentiation of U937 cells induced by phorbol‐myristate‐acetate or retinoic acid plus 1,25‐dihydroxy‐cholecalciferol by western blot, flow cytometry and immuno‐fluorescence. p25K (C3), p27K (IOTA) and p30/33K (C2) subunits were detected in both the nucleus and cytoplasm of undifferentiated cells. Flow cytometry demonstrated a biphasic decrease in proteasome subunits detection during differentiation induced by RA+VD. PMA caused an early transient decrease in these subunits followed by a return to their control level, except for p30/33K, which remained low. Immuno‐fluorescence also showed differences in the cytolocalization of the subunits, with a particular decrease in antigen labeling in the nucleus of RA+VD‐induced cells, and a scattering in the cytoplasm and a reorganization in the nucleus of PMA‐induced cells. Small amounts of proteasomal proteins were seen on the outer membrane of non‐induced cells; these membrane proteins disappeared when treated with RA+VD, whereas some increased on PMA‐induced cells. The differential changes in the distribution and type of proteasomes in RA+VD and PMA‐induced cells indicate that, possibly, 20S proteasomes may play a role in relation to the mechanisms of differentiation and the inducer used.

Stable Transfection of U937 Cells with Sense or Antisense RXR-α cDNA Suggests a Role for RXR-α in the Control of Monoblastic Differentiation Induced by Retinoic Acid and Vitamin D

1997 ◽  
Vol 236 (1) ◽  
pp. 94-102 ◽  
Author(s):  
Timothy R.P. Brown ◽  
Timothy J. Stonehouse ◽  
Joel S. Branch ◽  
Paul M. Brickell ◽  
David R. Katz
Keyword(s):  
Vitamin D ◽  
Retinoic Acid ◽  
Stable Transfection ◽  
U937 Cells

All-trans and 9-cis retinoic acid enhance 1,25-dihydroxyvitamin D3-induced monocytic differentiation of U937 cells

1996 ◽  
Vol 20 (8) ◽  
pp. 665-676 ◽  
Author(s):  
Hideaki Nakajima ◽  
Masahiro Kizaki ◽  
Hironori Ueno ◽  
Akihiro Muto ◽  
Nobuyuki Takayama ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
U937 Cells ◽  
Monocytic Differentiation ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3

The retinoic acid analog CBS-211A potentiates the 1α,25-dihydroxyvitamin D3-induced differentiation of U937 cells

1993 ◽  
Vol 38 (S1) ◽  
pp. 91-99 ◽  
Author(s):  
M. Taimi ◽  
H. Defacque ◽  
T. Commes ◽  
J. Favero ◽  
J. Dornand ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
U937 Cells ◽  
Induced Differentiation ◽  
Dihydroxyvitamin D3 ◽  
Acid Analog
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