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

Result code in 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>
Result on the web
<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>

Result language
angličtina
Original language name
Mifepristone potentiates etoposide toxicity in Hep G2 cells by modulating drug transport
Original language description
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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
<a href="/en/project/LO1304" target="_blank" >LO1304: Support of suistainability of the Institute of Molecular and Translational Medicine</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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