Melanoma is an aggressive cutaneous
cancer, whose incidence is growing in recent years, especially in the younger population. The favorable
therapy for this
neoplasm consists in its early surgical excision; otherwise, in case of late diagnosis,
melanoma becomes very refractory to any conventional
therapy. Nevertheless, the acute inflammatory response occurring after excision of the primary
melanoma can affect the activation and/or regulation of
melanoma invasion and
metastasis. Nonsteroidal anti-inflammatory drugs (
NSAIDs), widely employed in clinical
therapy as
cyclooxygenase inhibitors, also display a cytotoxic effect on some
cancer cell lines; therefore, their possible usage in combination with conventional chemo- and radio-
therapies of
tumors is being considered. In particular,
diclofenac, one of the most common
NSAIDs, displays its anti-proliferative effect in many
tumor lines, through an alteration of the cellular redox state. In this study, the possible anti-neoplastic potential of
diclofenac on the human
melanoma cell lines A2058 and SAN was investigated, and a comparison was made with the results obtained from the nonmalignant fibroblast cell line BJ-5ta. Either in A2058 or SAN, the
diclofenac treatment caused typical apoptotic morphological changes, as well as an increase of the number of sub-diploid nuclei; conversely, the same treatment on BJ-5ta had only a marginal effect. The observed decrease of Bcl-2/Bax ratio and a parallel increase of
caspase-3 activity confirmed the pro-apoptotic role exerted by
diclofenac in
melanoma cells; furthermore, the drug provoked an increase of the ROS levels, a decrease of mitochondrial
superoxide dismutase (SOD2), the cytosolic translocation of both SOD2 and
cytochrome c, and an increase of
caspase-9 activity. Finally, the cytotoxic effect of
diclofenac was amplified, in
melanoma cells, by the silencing of SOD2. These data improve the knowledge on the effects of
diclofenac and suggest that new anti-neoplastic treatments should be based on the central role of mitochondrion in
cancer development; under this concern, the possible involvement of SOD2 as a novel target could be considered.