Depleting tumor-NQO1 potentiates anoikis and inhibits growth of NSCLC

Brian Madajewski, Michael A. Boatman, Gaurab Chakrabarti, David A. Boothman, Erik A. Bey

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The fundamental role that NAD(P)H/quinone oxidoreductase 1 (NQO1) plays, in normal cells, as a cytoprotective enzyme guarding against stress induced by reactive oxygen species (ROS) is well documented. However, what is not known is whether the observed overexpression of NQO1 in neoplastic cells contributes to their survival. The current study discovered that depleting NQO1 expression in A549 and H292 lung adenocarcinoma cells caused an increase in ROS formation, inhibited anchorage-independent growth, increased anoikis sensitization, and decreased three-dimensional tumor spheroid invasion. These in vivo data further implicate tumor-NQO1 expression in a protumor survival role, because its depletion suppressed cell proliferation and decreased lung tumor xenograft growth. Finally, these data reveal an exploitable link between tumor-NQO1 expression and the survival of lung tumors because NQO1 depletion significantly decreased the percentage of ALDH(high) cancer cells within the tumor population. Implications: Loss of tumor-NQO1 expression inhibits tumor growth and suggests that novel therapeutics directed at tumor- NQO1 may have clinical benefit.

Original languageEnglish (US)
Pages (from-to)14-25
Number of pages12
JournalMolecular Cancer Research
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2016

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Anoikis
Growth
Neoplasms
Reactive Oxygen Species
Lung
Heterografts
NAD
Oxidoreductases

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

Depleting tumor-NQO1 potentiates anoikis and inhibits growth of NSCLC. / Madajewski, Brian; Boatman, Michael A.; Chakrabarti, Gaurab; Boothman, David A.; Bey, Erik A.

In: Molecular Cancer Research, Vol. 14, No. 1, 01.01.2016, p. 14-25.

Research output: Contribution to journalArticle

Madajewski, Brian ; Boatman, Michael A. ; Chakrabarti, Gaurab ; Boothman, David A. ; Bey, Erik A. / Depleting tumor-NQO1 potentiates anoikis and inhibits growth of NSCLC. In: Molecular Cancer Research. 2016 ; Vol. 14, No. 1. pp. 14-25.
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