Histone deacetylase inhibitors in plasma cell leukemia treatment: effect of bone marrow microenvironment

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10362309" target="_blank" >RIV/00216208:11110/17:10362309 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/17:10362309 RIV/00064190:_____/17:N0000083 RIV/00064165:_____/17:10362309

Výsledek na webu

<a href="http://dx.doi.org/10.4149/neo_2017_209" target="_blank" >http://dx.doi.org/10.4149/neo_2017_209</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.4149/neo_2017_209" target="_blank" >10.4149/neo_2017_209</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Histone deacetylase inhibitors in plasma cell leukemia treatment: effect of bone marrow microenvironment

Popis výsledku v původním jazyce

In the presented study we analysed the effect of histone deacetylase inhibitors (HDACi) suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) on human plasma cell leukemia (PCL) cell line UHKT-944 in the presence of bone marrow microenvironment (BMM). For the analysis, the cells were cultured alone, with bone marrow stromal cells (BMSCs), with extracellular matrix (ECM) components or with interleukin-6, and treated with varied concentrations of SAHA and VPA for 24/48 hours. To study the effect of HDACi, we investigated cell proliferation, apoptosis, cell cycle and changes in selected signalling pathways. We found that both SAHA and VPA induced apoptosis, but had no effect on the cell cycle distribution of UHKT-944 cells. Investigation of the antiproliferative effect of SAHA and VPA revealed that BMSCs and high concentration of interleukin-6 had partial protective effect against SAHA or both inhibitors, respectively. No effect of ECM components on the efficiency of HDACi was observed. We further revealed that VPA down-regulated STAT3 phosphorylation while both inhibitors decreased Akt phosphorylation. In conclusion, VPA and SAHA might represent an additional therapeutic strategy in the PCL treatment. Protective effect of BMM should be taken into account when investigating prospective therapeutic agents against plasma cell disorders.

Název v anglickém jazyce

Histone deacetylase inhibitors in plasma cell leukemia treatment: effect of bone marrow microenvironment

Popis výsledku anglicky

In the presented study we analysed the effect of histone deacetylase inhibitors (HDACi) suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) on human plasma cell leukemia (PCL) cell line UHKT-944 in the presence of bone marrow microenvironment (BMM). For the analysis, the cells were cultured alone, with bone marrow stromal cells (BMSCs), with extracellular matrix (ECM) components or with interleukin-6, and treated with varied concentrations of SAHA and VPA for 24/48 hours. To study the effect of HDACi, we investigated cell proliferation, apoptosis, cell cycle and changes in selected signalling pathways. We found that both SAHA and VPA induced apoptosis, but had no effect on the cell cycle distribution of UHKT-944 cells. Investigation of the antiproliferative effect of SAHA and VPA revealed that BMSCs and high concentration of interleukin-6 had partial protective effect against SAHA or both inhibitors, respectively. No effect of ECM components on the efficiency of HDACi was observed. We further revealed that VPA down-regulated STAT3 phosphorylation while both inhibitors decreased Akt phosphorylation. In conclusion, VPA and SAHA might represent an additional therapeutic strategy in the PCL treatment. Protective effect of BMM should be taken into account when investigating prospective therapeutic agents against plasma cell disorders.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Neoplasma

ISSN

0028-2685

e-ISSN

—

Svazek periodika

64

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

SK - Slovenská republika

Počet stran výsledku

12

Strana od-do

228-239

Kód UT WoS článku

000402091900009

EID výsledku v databázi Scopus

2-s2.0-85020455643