title: Renieramycin M Sensitizes Anoikis-resistant H460 Lung Cancer Cells to Anoikis.
abstract: OBJECTIVE
  Anoikis resistance plays a crucial role in the promotion of survival of circulating tumor cells. This study aimed to evaluate the mechanistic pathways of anoikis resistance in human lung cancer cells and test the possible therapeutic effect of renieramycin M (RM) from the sponge Xestospongia sp. in conversion of anoikis resistance.
  
  
  METHODS
  Anoikis-resistant H460 (AR_H460) lung cancer cells in a detached condition were treated with RM at subtoxic concentrations for 24 h. Cell viability, cell morphology, and expression of the proteins involved in survival and apoptotic pathways were determined.
  
  
  RESULTS
  Anoikis resistance in H460 cells is mediated through the up-regulation of survival and anti-apoptotic proteins, namely phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated ATP-dependent tyrosine kinase (p-AKT), B-cell lymphoma-2 (BCL2), and myeloid cell leukemia-1 (MCL1). RM significantly reduced cell viability and inhibited spontaneous aggregation of AR_H460 cells. Western blot analysis revealed that RM suppressed the levels of survival proteins p-ERK and p-AKT and anti-apoptotic proteins BCL2 and MCL1.
  
  
  CONCLUSIONS
  RM is a potential anti-metastatic agent by sensitizing anoikis-resistant lung cancer cells to anoikis by the suppression of anoikis-resistance mechanisms.
authors.affiliation: Center for Bioactive Natural Products from Marine Organisms and Endophytic Fungi, Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Pathumwan, Bangkok, Thailand.
authors.forename: Natchanun
authors.initials: N
authors.lastname: Sirimangkalakitti
authors.affiliation: Center for Bioactive Natural Products from Marine Organisms and Endophytic Fungi, Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Pathumwan, Bangkok, Thailand.
authors.forename: Supakarn
authors.initials: S
authors.lastname: Chamni
authors.affiliation: Center for Bioactive Natural Products from Marine Organisms and Endophytic Fungi, Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Pathumwan, Bangkok, Thailand pithi_chan@yahoo.com khanit.s@pharm.chula.ac.th.
authors.forename: Khanit
authors.initials: K
authors.lastname: Suwanborirux
authors.affiliation: Cell-Based Drug and Health Product Development Research Unit, Chulalongkorn University, Pathumwan, Bangkok, Thailand Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Pathumwan, Bangkok, Thailand pithi_chan@yahoo.com khanit.s@pharm.chula.ac.th.
authors.forename: Pithi
authors.initials: P
authors.lastname: Chanvorachote
mesh_terms: D023102:Anoikis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; C000595707:BCL2 protein, human; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D044005:Tetrahydroisoquinolines; C482478:renieramycin M; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Renieramycin M; anoikis resistance; anoikis-sensitizing activity; anti-matastasis; lung cancer