1212 Depletion of ARMS in melanoma cells induces autophagy-mediated cell death under oxidative stress

Oxidative stress has been recognized to be associated with melanoma. We have previously shown that ankyrin repeat-rich membrane spanning (ARMS), a tetra-spanning transmembrane protein, was overexpressed in melanoma cells and conferred resistance hydrogen peroxide (H2O2)-induced cell death. To explore the molecular mechanism of ARMS under oxidative stress, we established ARMS-knockdown (siARMS) challenged them H2O2. found depletion increased levels reactive oxygen species (ROS) which contributed augmented autophagic flux H2O2 treatment. H2O2-mediated autophagy resulted non-apoptotic cellular demise siARMS cells, as cytoprotective effects were achieved by pretreatment inhibitor bafilomycin A1 or knockdown autophagy-related 5 (ATG5). Accordingly, reducing ROS antioxidants diminished concomitant attenuation In addition, inhibited H2O2-induced activation nuclear factor-kappa B signaling pathway repressed expression antioxidant proteins catalase SOD1 cells. Our results suggest silencing an alternative therapeutic strategy treating apoptosis-resistant melanomas activating ROS-induced autophagy-mediated