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Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39): A Gene Expression Study.

Savlı H, Galimberti S, Sünnetçi D, Canesastraro M, Palumbo G, Nagy B, Di Raimondo F, Petrini M - Turk J Haematol (2015)

Bottom Line: Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment.Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene.Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings.

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39.

Methods: Oligonucleotide microarray platforms were used for gene expression and pathway analysis. Confirmation studies were performed using quantitative real time PCR.

Results: Bortezomib treatment has shown upregulated DIABLO and NF-κBIB (a NF-κB inhibitor) and downregulated NF-κB1, NF-κB2, and BIRC1 gene expressions. Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment. Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene. Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings.

Discussion and conclusion: Results support the suggestions about possible use of proteasome inhibitors in the treatment of high-risk myelodysplastic syndrome (MDS). NF-κB was observed as an important modulator in leukemic transformation of MDS.

No MeSH data available.


Related in: MedlinePlus

Bortezomib exerted a significant anti-proliferative effect in a dose and time-dependent manner.
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f1: Bortezomib exerted a significant anti-proliferative effect in a dose and time-dependent manner.

Mentions: Bortezomib inactivated NF-kB and exerted an anti-proliferative (Figure 1) and pro-apoptotic effect (Figure 2) by blocking cell cycle in the G2 phase (Figure 3). It increased the release of reactive oxygen species (Figure 4) and down-regulated the WT1 expression (Figure 5). In the untreated P39, 84 of the 93 genes involved in the apoptosis pathway and representation in the Taqman Low-Density Arrays were expressed. After treatment, bortezomib had up-regulated DIABLO and NFkBIB (NF-kB inhibitor), and down-regulated the NF-kB1, NF-kB2, and BIRC1, an anti-apoptotic gene (Figure 5). Seven gene pathways (P53, PPAR, IL6, IL2, hypoxia, Huntington’s disease, TLR) were found most significantly de-regulated in our microarray analysis.


Bortezomib and Arsenic Trioxide Activity on a Myelodysplastic Cell Line (P39): A Gene Expression Study.

Savlı H, Galimberti S, Sünnetçi D, Canesastraro M, Palumbo G, Nagy B, Di Raimondo F, Petrini M - Turk J Haematol (2015)

Bortezomib exerted a significant anti-proliferative effect in a dose and time-dependent manner.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4563195&req=5

f1: Bortezomib exerted a significant anti-proliferative effect in a dose and time-dependent manner.
Mentions: Bortezomib inactivated NF-kB and exerted an anti-proliferative (Figure 1) and pro-apoptotic effect (Figure 2) by blocking cell cycle in the G2 phase (Figure 3). It increased the release of reactive oxygen species (Figure 4) and down-regulated the WT1 expression (Figure 5). In the untreated P39, 84 of the 93 genes involved in the apoptosis pathway and representation in the Taqman Low-Density Arrays were expressed. After treatment, bortezomib had up-regulated DIABLO and NFkBIB (NF-kB inhibitor), and down-regulated the NF-kB1, NF-kB2, and BIRC1, an anti-apoptotic gene (Figure 5). Seven gene pathways (P53, PPAR, IL6, IL2, hypoxia, Huntington’s disease, TLR) were found most significantly de-regulated in our microarray analysis.

Bottom Line: Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment.Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene.Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings.

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: We aimed to understand the molecular pathways affected by bortezomib and arsenic trioxide treatment on myelomonocytoid cell line P39.

Methods: Oligonucleotide microarray platforms were used for gene expression and pathway analysis. Confirmation studies were performed using quantitative real time PCR.

Results: Bortezomib treatment has shown upregulated DIABLO and NF-κBIB (a NF-κB inhibitor) and downregulated NF-κB1, NF-κB2, and BIRC1 gene expressions. Combination treatment of the two compounds showed gene expression deregulations in concordance by the results of single bortezomib treatment. Especially, P53 was a pathway more significantly modified and a gene network centralized around the beta estradiol gene. Beta estradiol, BRCA2, and FOXA1 genes were remarkable deregulations in our findings.

Discussion and conclusion: Results support the suggestions about possible use of proteasome inhibitors in the treatment of high-risk myelodysplastic syndrome (MDS). NF-κB was observed as an important modulator in leukemic transformation of MDS.

No MeSH data available.


Related in: MedlinePlus