title: Sub-toxic cisplatin mediates anoikis resistance through hydrogen peroxide-induced caveolin-1 up-regulation in non-small cell lung cancer cells.
abstract: BACKGROUND
  Exposure to inadequate chemotherapy may alter cancer cell behavior including their metastatic potential. Because the molecular basis of such a phenomenon is largely unclear, we investigated the possible impact of cisplatin on anoikis response on human lung carcinoma cells.
  
  
  METHODS
  Using molecular and pharmacological tools, Caveolin-1 (CAV1) overexpressing and knock-down H460 cells were generated by stable transfection. The levels of CAV1 were determined by western blotting and reactive oxygen species (ROS) were detected by specific probes.
  
  
  RESULTS
  Sub-toxic concentrations of cisplatin suppressed anoikis response in H460 cells. The anoikis attenuation observed, was found to be caused by CAV1 up-regulation. Exposure to cisplatin induced superoxide anion and hydrogen peroxide generation; however, only hydrogen peroxide was found to be responsible for the CAV1 elevation.
  
  
  CONCLUSIONS
  Exposure to cisplatin at sub-toxic concentrations induced hydrogen peroxide generation and the subsequent increase of ROS further regulated CAV1 levels and anoikis resistance. Our findings demonstrate a novel effect of cisplatin treatment on cancer cells which may lead to a better understanding of cancer biology and in the improvement of chemotherapy.
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Phatumwan, Bangkok, Thailand 10330.
authors.forename: Thitiporn
authors.initials: T
authors.lastname: Songserm
authors.forename: Varisa
authors.initials: V
authors.lastname: Pongrakhananon
authors.forename: Pithi
authors.initials: P
authors.lastname: Chanvorachote
mesh_terms: D023102:Anoikis / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D051242:Caveolin 1 / Q000032:analysis / Q000502:physiology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D051242:Caveolin 1; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002945:Cisplatin