TY - JOUR
T1 - Depleting tumor-NQO1 potentiates anoikis and inhibits growth of NSCLC
AU - Madajewski, Brian
AU - Boatman, Michael A.
AU - Chakrabarti, Gaurab
AU - Boothman, David A.
AU - Bey, Erik A.
N1 - Funding Information:
The authors thank the laboratories of Scot A. Weed, Michael J. Ruppert, and Steven M. Frisch for their timely help in developing our invasion, soft-agar, and anoikis protocols, respectively. They thank the WVU Flow Cytometry core for their technical assistance with Flow Cytometry experiments. They also thank the laboratory of Dr. John D. Minna for the use of their Human Bronchial Epithelial Cells. This work was supported in part by grants awarded to the Principal Investigator E.A. Bey fromWV-CTSI (NIH-NIGMS U54 GM104942) and ACS (IRG-09-061-04). This work was also supported in part by NIH grant CA102792-13 to D.A. Boothman. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Publisher Copyright:
©2015 AACR.
PY - 2016/1
Y1 - 2016/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1541-7786.MCR-15-0207-T
DO - 10.1158/1541-7786.MCR-15-0207-T
M3 - Article
C2 - 26553038
AN - SCOPUS:84954511122
SN - 1541-7786
VL - 14
SP - 14
EP - 25
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 1
ER -