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CGP74514A Enhances TRAIL-induced Apoptosis in Breast Cancer Cells by Reducing X-linked Inhibitor of Apoptosis Protein
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SYSNO ASEP 0434374 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title CGP74514A Enhances TRAIL-induced Apoptosis in Breast Cancer Cells by Reducing X-linked Inhibitor of Apoptosis Protein Author(s) Park, S. (KR)
Shim, S.M. (KR)
Nam, S.H. (KR)
Anděra, Ladislav (UMG-J) RID
Suh, N. (KR)
Kim, I. (KR)Source Title Anticancer Research. - : International Institute of Anticancer Research - ISSN 0250-7005
Roč. 34, č. 7 (2014), s. 3557-3562Number of pages 6 s. Language eng - English Country GR - Greece Keywords TRAIL ; Apoptosis ; Breast carcinom Subject RIV EB - Genetics ; Molecular Biology Subject RIV - cooperation Genetics ; Molecular Biology R&D Projects LH12202 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support UMG-J - RVO:68378050 UT WOS 000338780300043 Annotation 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. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2015
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