CASP8 and neoplasm: The release of Cu into tumor cells enhances reactive oxygen species (ROS) as well as nitric oxide (NO) production, which results in DNA fragmentation, induces pro-apoptotic protein upregulation such as Bax, and enhances caspase-3, caspase-8, and caspase-9 generation that motivates cancer cells apoptosis [68] even in solid tumor hypoxic condition [69].