Reactive oxygen species in melanoma and its therapeutic implications

Oxidative phosphorylation in the mitochondria is an important energy-producing process for eukaryotic cells, but this process can also result in producing potentially cell-damaging side products. Oxygen is the final proton acceptor in this cascade of electron/proton transfer and results in harmless water. The electron transfer, however, is not completely efficient and results in the production of reactive oxygen species (ROS). Low amounts of these ROS are important for cellular-signalling pathways. Excessive ROS, however, can induce cell damage that can culminate in cell death. Therefore, the cell has developed an antioxidant network to scavenge excessively produced ROS. In general, the balance between the production and scavenging of ROS leads to homeostasis. Disturbance of this equilibrium can alter normal cellular processes; it often occurs in tumour cells. In this review, the role of ROS in cutaneous melanoma development and progression is described. Cutaneous melanoma arises from epidermal melanocytes in skin, which is a relatively hypoxic tissue. ROS are generated as a result of increased metabolism of transformed cells, immune reaction against the developing tumour, ultraviolet radiation, melanin production and an altered antioxidant system. Knowledge of the role of ROS in melanoma development and the mechanisms that alleviate oxidative stress can aid in the development of better antimelanoma therapies.