title: In vitro oxygen availability modulates the effect of artesunate on HeLa cells.
abstract: OBJECTIVE
  Hypoxia can affect chemotherapeutic drug efficacy in cancer patients, yet related in vitro assays in oxygen-rich environment remain the norm. Such levels are well beyond normoxic/hypoxic levels typically experienced by normal tissues/tumor masses. The present study evaluated how artesunate anti-tumor efficacy is modulated by oxygen availability in HeLa cells and its implications for future in vitro analyses.
  
  
  METHODS
  Real-time cell analysis was employed to evaluate HeLa cell toxicity to artesunate at 21%, 4% or 1% oxygen. Cell count analysis was performed to validate real-time data.
  
  
  RESULTS
  An increase in artesunate efficacy was observed when oxygen concentration was reduced from atmospheric levels down to in vivo-relevant levels.
  
  
  CONCLUSIONS
  Artesunate is more potent than originally reported using standard oxygen conditions during in vitro studies. The inclusion of this long overlooked variable as standard in future in vitro analysis procedures is warranted.
authors.affiliation: Mitochondrial Biology & Radiation Research Centre, Department of Life Sciences, Institute of Technology Sligo, Sligo, Ireland.
authors.forename: James
authors.initials: J
authors.lastname: Murray
authors.affiliation: MSA Laboratory, Focas Institute, Dublin Institute of Technology, Dublin, Ireland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gannon
authors.affiliation: School of Chemical and Pharmaceutical Sciences, Dublin Institute of Technology, Dublin, Ireland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rawe
authors.affiliation: Mitochondrial Biology & Radiation Research Centre, Department of Life Sciences, Institute of Technology Sligo, Sligo, Ireland murphy.james@itsligo.ie.
authors.forename: James E J
authors.initials: JE
authors.lastname: Murphy
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D017097:Electric Impedance; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D000077332:Artesunate; D010100:Oxygen
keywords: HeLa cells; Oxygen-rich enviroment; artesunate; hypoxia; in vitro study