A novel bioluminescent bacterial biosensor for measurement of Ara-CTP and cytarabine potentiation by fludarabine in seven leukaemic cell lines

Leuk Res. 2013 Jun;37(6):690-6. doi: 10.1016/j.leukres.2013.02.012. Epub 2013 Mar 7.

Abstract

This study evaluates an in vitro biosensor assay capable of detecting the intracellular levels of the tri-phosphorylated form of cytarabine (Ara-CTP) within one working day. The biosensor predicted the response of seven leukaemic cell lines with varying known sensitivities to cytarabine alone and in combination with fludarabine. High-performance liquid chromatography (HPLC), 3-day assessment of cellular viable mass, and flow cytometric assessment of apoptosis were used to validate biosensor performance. A correlation between the biosensor results and Ara-CTP quantitation by HPLC was confirmed (R=0.972). The biosensor was also capable of detecting enhanced accumulation of Ara-CTP following sequential pre-treatment of leukaemic cells with cytarabine ± fludarabine.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Arabinofuranosylcytosine Triphosphate / analysis*
  • Bacterial Proteins / analysis
  • Biosensing Techniques / methods*
  • Cell Line, Tumor
  • Cytarabine / pharmacology*
  • HL-60 Cells
  • Humans
  • K562 Cells
  • Leukemia / diagnosis
  • Leukemia / drug therapy
  • Leukemia / pathology*
  • Luminescent Measurements / methods
  • Luminescent Proteins / analysis
  • Treatment Outcome
  • Vidarabine / analogs & derivatives*
  • Vidarabine / pharmacology

Substances

  • Bacterial Proteins
  • Luminescent Proteins
  • Cytarabine
  • Arabinofuranosylcytosine Triphosphate
  • Vidarabine
  • fludarabine