CGP74514A enhances TRAIL-induced apoptosis in breast cancer cells by reducing X-linked inhibitor of apoptosis protein.

CGP74514A enhances TRAIL-induced apoptosis in breast cancer cells by reducing X-linked inhibitor of apoptosis protein.

Anticancer research (2014-07-02)

Sojung Park, Sang-Mi Shim, Sang-Hee Nam, Ladislav Andera, Nayoung Suh, Inki Kim

ABSTRACT

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. 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. 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. CGP74514A sensitized breast cancer cells to TRAIL via reduction of XIAP expression level.

MATERIALS

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