The present study was designed to demystify the mechanistic basis and interrelationship of ER stress and autophagy in cell death by examining and looking for the changes in the PERK–ATF4–C/EBP Homologous Protein (CHOP) and MAPK and PI3K/AKT signaling pathway axes regulating cellular proliferation and death processes and evaluating their role as therapeutic targets for NPC-402 treatment to achieve an anti-melanoma effect. This evidence concerns the gene DDIT3 and melanoma.