CGP74514A Enhances TRAIL-induced Apoptosis in Breast Cancer Cells by Reducing X-linked Inhibitor of Apoptosis Protein

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F14%3A00434374" target="_blank" >RIV/68378050:_____/14:00434374 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

CGP74514A Enhances TRAIL-induced Apoptosis in Breast Cancer Cells by Reducing X-linked Inhibitor of Apoptosis Protein

Popis výsledku v původním jazyce

Background: Despite the selectivity of Tumor necrosis factor Related Apoptosis-Inducing Ligand (TRAIL) for cancer cell killing activity, breast cancer cells are resistant to TRAIL-induced apoptosis for various reasons. Materials and Methods: From a functionally-characterized small-molecule dataset, CGP74514A was identified as a TRAIL sensitizer in MCF-7 breast cancer cells. Combination of sub-toxic dose of TRAIL with CGP74514A was evaluated in three TRAIL-resistant breast cancer cells, MCF-7, T47D and SK-BR-3. Results: In all tested cells, CGP74514A enhanced TRAIL sensitivity. Combination treatment triggered apoptotic events faster than single treatment. Regarding its mechanism of action, CGP74514A reduced cytosolic X-linked inhibitor of apoptosis protein (XIAP). Small interfering RNA-mediated knockdown experiments showed that reduction of XIAP is the reason of sensitization. Conclusion: CGP74514A sensitized breast cancer cells to TRAIL via reduction of XIAP expression level.

Název v anglickém jazyce

CGP74514A Enhances TRAIL-induced Apoptosis in Breast Cancer Cells by Reducing X-linked Inhibitor of Apoptosis Protein

Popis výsledku anglicky

Background: Despite the selectivity of Tumor necrosis factor Related Apoptosis-Inducing Ligand (TRAIL) for cancer cell killing activity, breast cancer cells are resistant to TRAIL-induced apoptosis for various reasons. Materials and Methods: From a functionally-characterized small-molecule dataset, CGP74514A was identified as a TRAIL sensitizer in MCF-7 breast cancer cells. Combination of sub-toxic dose of TRAIL with CGP74514A was evaluated in three TRAIL-resistant breast cancer cells, MCF-7, T47D and SK-BR-3. Results: In all tested cells, CGP74514A enhanced TRAIL sensitivity. Combination treatment triggered apoptotic events faster than single treatment. Regarding its mechanism of action, CGP74514A reduced cytosolic X-linked inhibitor of apoptosis protein (XIAP). Small interfering RNA-mediated knockdown experiments showed that reduction of XIAP is the reason of sensitization. Conclusion: CGP74514A sensitized breast cancer cells to TRAIL via reduction of XIAP expression level.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/LH12202" target="_blank" >LH12202: Analýza a potlačení mechanismů vedoucích k resistenci nádorových buněk k ligandu TRAIL.</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

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

Název periodika

Anticancer Research

ISSN

0250-7005

e-ISSN

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Svazek periodika

34

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

GR - Řecká republika

Počet stran výsledku

6

Strana od-do

3557-3562

Kód UT WoS článku

000338780300043

EID výsledku v databázi Scopus

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