The role of UVA radiation in ketoprofen-mediated BRAF-mutant amelanotic melanoma cells death - A study at the cellular and molecular level

Abstract

Malignant melanoma is the cause of 80% of deaths in skin cancer patients. Treatment of melanoma in the 4th stage of clinical advancement, in which inoperable metastasis occur, does not provide sufficient effects. Ketoprofen has phototoxic properties and it can be used as a new treatment option for skin cancers as a part of photochemotherapy. The present study was designed to investigate whether ketoprofen in combination with UVA induces cytotoxic, anti-proliferative and pro-apoptotic effects on melanoma cells. It was stated that co-treatment with 1.0 mM ketoprofen and UVA irradiation disturbed homeostasis of C32 melanoma cells by lowering its vitality (decrease of GSH level). Contrary to C32 cells, melanocytes showed low sensitivity to ketoprofen and UVA radiation, pointing selectivity in the mode of action towards melanoma cells. Co-treatment with ketoprofen and UVA irradiation has cytotoxic and anti-proliferative and pro-apoptotic effect on C32. The co-treatment triggered the DNA fragmentation and changed the cell cycle in C32 cells. In conclusion, it could be stated that local application of ketoprofen in combination with UVA irradiation may be used to support the treatment of melanoma and creates the possibility of reducing the risk of cancer recurrence and metastasis.

Keywords: GSH; Ketoprofen; Melanoma; UVA.