title: Depleting Tumor-NQO1 Potentiates Anoikis and Inhibits Growth of NSCLC.
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.
  
  
  CONCLUSIONS
  Loss of tumor-NQO1 expression inhibits tumor growth and suggests that novel therapeutics directed at tumor-NQO1 may have clinical benefit.
authors.affiliation: Department of Pharmaceutical Sciences, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506.
authors.forename: Brian
authors.initials: B
authors.lastname: Madajewski
authors.affiliation: Department of Pharmaceutical Sciences, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Boatman
authors.affiliation: Department of Pharmacology, Laboratory of Molecular Cell Stress Responses, Program in Cell Stress and Cancer Nanomedicine, Simmons Cancer Center, UT Southwestern Medical Center at Dallas, TX 75390-8807.
authors.forename: Gaurab
authors.initials: G
authors.lastname: Chakrabarti
authors.affiliation: Department of Pharmacology, Laboratory of Molecular Cell Stress Responses, Program in Cell Stress and Cancer Nanomedicine, Simmons Cancer Center, UT Southwestern Medical Center at Dallas, TX 75390-8807.
authors.forename: David A
authors.initials: DA
authors.lastname: Boothman
authors.affiliation: Department of Pharmaceutical Sciences, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Bey
mesh_terms: D000818:Animals; D023102:Anoikis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D001728:Dicumarol / Q000008:administration & dosage* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors*; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D001728:Dicumarol; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human