In vitro oxygen availability modulates the effect of artesunate on HeLa cells

Anticancer Res. 2014 Dec;34(12):7055-60.

Abstract

Background/aim: 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.

Materials and 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.

Conclusion: 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.

Keywords: HeLa cells; Oxygen-rich enviroment; artesunate; hypoxia; in vitro study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Artemisinins / therapeutic use*
  • Artesunate
  • Cell Adhesion / drug effects
  • Cell Count
  • Cell Hypoxia
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm*
  • Electric Impedance
  • HeLa Cells
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Oxygen / metabolism*

Substances

  • Antineoplastic Agents
  • Artemisinins
  • Artesunate
  • Oxygen