title: CGP74514A enhances TRAIL-induced apoptosis in breast cancer cells by reducing X-linked inhibitor of apoptosis protein.
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.
  
  
  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.
  
  
  CONCLUSIONS
  CGP74514A sensitized breast cancer cells to TRAIL via reduction of XIAP expression level.
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors: Sojung
authors: S
authors: Park
authors: Department of Biomedical Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Sang-Mi
authors: SM
authors: Shim
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors: Sang-Hee
authors: SH
authors: Nam
authors: Institute of Molecular Genetics, Academy of Science of the Czech Republic, Prague, Czech Republic.
authors: Ladislav
authors: L
authors: Andera
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea Department of Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Nayoung
authors: N
authors: Suh
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea Department of Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea Cell Dysfunction Research Center (CDRC), University of Ulsan College of Medicine, Seoul, Republic of Korea ik.kim@amc.seoul.kr.
authors: Inki
authors: I
authors: Kim
mesh_terms: D015075:2-Aminopurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage / Q000494:pharmacology*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: C469937:N(2)-(2-aminocyclohexyl)-N(6)-(3-chlorophenyl)-9-ethyl-9H-purine-2,6-diamine; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D015075:2-Aminopurine
keywords: CGP74514A; TRAIL; XIAP; breast cancer