Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 3557-3562 |
| Number of pages | 6 |
| Journal | Anticancer Research |
| Volume | 34 |
| Issue number | 7 |
| State | Published - 1 Jul 2014 |
Keywords
- Breast cancer
- CGP74514A
- TRAIL
- XIAP
