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Depleting Tumor-NQO1 Potentiates Anoikis and Inhibits Growth of NSCLC.
Madajewski, Brian; Boatman, Michael A; Chakrabarti, Gaurab; Boothman, David A; Bey, Erik A.
Afiliação
  • Madajewski B; Department of Pharmaceutical Sciences, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506.
  • Boatman MA; Department of Pharmaceutical Sciences, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506.
  • Chakrabarti G; 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.
  • Boothman DA; 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.
  • Bey EA; Department of Pharmaceutical Sciences, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506.
Mol Cancer Res ; 14(1): 14-25, 2016 Jan.
Article em En | MEDLINE | ID: mdl-26553038
UNLABELLED: 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dicumarol / NAD(P)H Desidrogenase (Quinona) / Carcinoma Pulmonar de Células não Pequenas / Inibidores Enzimáticos / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Mol Cancer Res Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dicumarol / NAD(P)H Desidrogenase (Quinona) / Carcinoma Pulmonar de Células não Pequenas / Inibidores Enzimáticos / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Mol Cancer Res Ano de publicação: 2016 Tipo de documento: Article