title: Artonin E mediates MCL1 down-regulation and sensitizes lung cancer cells to anoikis.
abstract: BACKGROUND
  Anoikis, or detachment-induced apoptosis, is recognized as a key inhibitory process of cancer metastasis. Since lung cancer cells possess an ability to resist anoikis, resulting in a high rate of metastasis and death, the present study aimed to investigate the possible anoikis-sensitizing effect of artonin E (AE).
  
  
  METHODS
  AE was extracted from bark of Artocarpus gomezianus. Anoikis sensitization of AE was investigated in H460, A549 and H292 human lung cancer cells. The level of anoikis-related proteins was determined by western blot analysis and viable cells were measured by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method.
  
  
  RESULTS
  AE was shown to enhance anoikis of H460 cells in a dose-dependent manner. We investigated the underlying mechanisms of AE on anoikis sensitization and found that AE sensitized the cells by down-regulating the anti-apoptotic myeloid leukemia cell sequence-1 (MCL1) protein but had no significant effect on other proteins of the B-cell lymphoma-2 (BCL2) family, including BCL2 and BCL2-associated X protein (BAX). Anoikis sensitization of AE was consistently observed in A549 and H292 lung cancer cells.
  
  
  CONCLUSIONS
  The present study demonstrates a novel activity of AE on lung cancer cell anoikis for the first time which might lead to the development of a new strategy for lung cancer therapy.
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulakongkorn University, Phatumwan, Bangkok, 10330 Thailand.
authors.forename: Ekkarat
authors.initials: E
authors.lastname: Wongpankam
authors.forename: Preedakorn
authors.initials: P
authors.lastname: Chunhacha
authors.forename: Varisa
authors.initials: V
authors.lastname: Pongrakhananon
authors.forename: Boonchoo
authors.initials: B
authors.lastname: Sritularak
authors.forename: Pithi
authors.initials: P
authors.lastname: Chanvorachote
mesh_terms: D023102:Anoikis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; C066727:artonin E