Depleting Tumor-NQO1 Potentiates Anoikis and Inhibits Growth of NSCLC

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The fundamental role that NAD(P)H/quinone oxidoreductase 1 (NQO1) plays, in normal cells, as a cyto-protective 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 3-D tumor-spheroid invasion. These in vivo data further implicate tumor-NQO1 expression in a pro-tumor survival role, since 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 since NQO1 depletion significantly decreased the percentage of ALDH(high) cancer cells within the tumor population.