Following anticancer drug activity in cell lysates with DNA devices

Dimithree Kahanda, Naveen Singh, David A. Boothman, Jason D. Slinker

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

There is a great need to track the selectivity of anticancer drug activity and to understand the mechanisms of associated biological activity. Here we focus our studies on the specific NQO1 bioactivatable drug, ß-lapachone, which is in several Phase I clinical trials to treat human non-small cell lung, pancreatic and breast cancers. Multi-electrode chips with electrochemically-active DNA monolayers are used to track anticancer drug activity in cellular lysates and correlate cell death activity with DNA damage. Cells were prepared from the triple-negative breast cancer (TNBC) cell line, MDA-MB-231 (231) to be proficient or deficient in expression of the NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme, which is overexpressed in most solid cancers and lacking in control healthy cells. Cells were lysed and added to chips, and the impact of β-lapachone (β-lap), an NQO1-dependent DNA-damaging drug, was tracked with DNA electrochemical signal changes arising from drug-induced DNA damage. Electrochemical DNA devices showed a 3.7-fold difference in the electrochemical responses in NQO1+ over NQO1− cell lysates, as well as 10–20-fold selectivity to catalase and dicoumarol controls that deactivate DNA damaging pathways. Concentration-dependence studies revealed that 1.4 µM β-lap correlated with the onset of cell death from viability assays and the midpoint of DNA damage on the chip, and 2.5 µM β-lap correlated with the midpoint of cell death and the saturation of DNA damage on the chip. Results indicate that these devices could inform therapeutic decisions for cancer treatment.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalBiosensors and Bioelectronics
Volume119
DOIs
StatePublished - Nov 15 2018

Keywords

  • Diagnostic
  • DNA damage
  • DNA repair
  • Drug assay
  • Drug screening
  • Electrochemical biosensing

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Biomedical Engineering
  • Electrochemistry

Fingerprint Dive into the research topics of 'Following anticancer drug activity in cell lysates with DNA devices'. Together they form a unique fingerprint.

  • Cite this