Mifepristone potentiates etoposide toxicity in Hep G2 cells by modulating drug transport

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F19%3A73594108" target="_blank" >RIV/61989592:15110/19:73594108 - isvavai.cz</a>

Výsledek na webu

<a href="https://reader.elsevier.com/reader/sd/pii/S0887233318305484?token=BECE2B476D45B5CF413ACC0F16795AE0B8E33B77605198A8B90E8B88C2751C18C553A0BA7373A1271B2B6858CB152087" target="_blank" >https://reader.elsevier.com/reader/sd/pii/S0887233318305484?token=BECE2B476D45B5CF413ACC0F16795AE0B8E33B77605198A8B90E8B88C2751C18C553A0BA7373A1271B2B6858CB152087</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tiv.2018.09.005" target="_blank" >10.1016/j.tiv.2018.09.005</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mifepristone potentiates etoposide toxicity in Hep G2 cells by modulating drug transport

Popis výsledku v původním jazyce

Etoposide is a well-known and widely used anticancer drug that displays several side effects. In addition, tumors often acquire resistance to this drug. Our aim is to develop a combination therapy that would augment toxicity of etoposide in malignant cells. Based on literature and our experiments, we selected mifepristone (RU486) as a potential supporting molecule that is able to enhance etoposide toxicity against cancer cells. All experiments were performed with Hep G2 cells, a well-known and described human hepatocellular carcinoma cell line. By using xCELLigence system, we demonstrated that mifepristone enhances toxicity of etoposide in a dose dependent manner with concomitant caspase-3 activity. We evaluated upregulation of Bax because mifepristone was demonstrated to modulate proapoptotic Bax protein expression. Our data show only weak and not statistically significant increase of Bax expression. On the other hand, we show that mifepristone increases etoposide toxicity via inhibition of ABC transporters, coupled with significant increase of intracellular etoposide concentration. In conclusion, we demonstrate that mifepristone has a synergistic effect with etoposide treatment in the Hep G2 cells and that the effect is related to ABC transporters inhibition.

Název v anglickém jazyce

Mifepristone potentiates etoposide toxicity in Hep G2 cells by modulating drug transport

Popis výsledku anglicky

Etoposide is a well-known and widely used anticancer drug that displays several side effects. In addition, tumors often acquire resistance to this drug. Our aim is to develop a combination therapy that would augment toxicity of etoposide in malignant cells. Based on literature and our experiments, we selected mifepristone (RU486) as a potential supporting molecule that is able to enhance etoposide toxicity against cancer cells. All experiments were performed with Hep G2 cells, a well-known and described human hepatocellular carcinoma cell line. By using xCELLigence system, we demonstrated that mifepristone enhances toxicity of etoposide in a dose dependent manner with concomitant caspase-3 activity. We evaluated upregulation of Bax because mifepristone was demonstrated to modulate proapoptotic Bax protein expression. Our data show only weak and not statistically significant increase of Bax expression. On the other hand, we show that mifepristone increases etoposide toxicity via inhibition of ABC transporters, coupled with significant increase of intracellular etoposide concentration. In conclusion, we demonstrate that mifepristone has a synergistic effect with etoposide treatment in the Hep G2 cells and that the effect is related to ABC transporters inhibition.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LO1304" target="_blank" >LO1304: Podpora udržitelnosti Ústavu molekulární a translační medicíny</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

TOXICOLOGY IN VITRO

ISSN

0887-2333

e-ISSN

—

Svazek periodika

54

Číslo periodika v rámci svazku

February

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

33-40

Kód UT WoS článku

000454467300004

EID výsledku v databázi Scopus

2-s2.0-85053499072