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

Sojung Park, Sang M.I. Shim, Sang Hee Nam, Ladislav Andera, Nayoung Suh, Inki Kim

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 languageEnglish
Pages (from-to)3557-3562
Number of pages6
JournalAnticancer Research
Volume34
Issue number7
StatePublished - 1 Jul 2014

Keywords

  • Breast cancer
  • CGP74514A
  • TRAIL
  • XIAP

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