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

0434374 - ÚMG 2015 RIV GR eng J - Článek v odborném periodiku
Park, S. - Shim, S.M. - Nam, S.H. - Anděra, Ladislav - Suh, N. - Kim, I.
CGP74514A Enhances TRAIL-induced Apoptosis in Breast Cancer Cells by Reducing X-linked Inhibitor of Apoptosis Protein.
Anticancer Research. Roč. 34, č. 7 (2014), s. 3557-3562. ISSN 0250-7005. E-ISSN 1791-7530
Grant CEP: GA MŠMT LH12202
Institucionální podpora: RVO:68378050
Klíčová slova: TRAIL * Apoptosis * Breast carcinom
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 1.826, rok: 2014

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.
Trvalý link: http://hdl.handle.net/11104/0238463