Abstract
Malignant melanoma is responsible for the majority of skin cancer-related deaths. The methods of cancer treatment include surgical removal, chemotherapy, immunotherapy, and targeted therapy. However, neither of these methods gives satisfactory results. Therefore, the development of new anticancer therapeutic strategies is very important and may extend the life span of people suffering from melanoma. The aim of this study was to examine the effect of ketoprofen (KTP) and UVA radiation (UVAR) therapy on cell proliferation, apoptosis, and cell cycle distribution in both melanotic melanoma cells (COLO829) and human melanocytes (HEMn-DP) in relation to its supportive effect in the treatment of melanoma. The therapy combining the use of pre-incubation with KTP and UVAR causes a significant increase in the anti-proliferative properties of ketoprofen towards melanoma cells and the co-exposure of melanotic melanoma cells induced apoptosis shown as the mitochondrial membrane breakdown, cell-cycle deregulation, and DNA fragmentation. Moreover, co-treatment led to GSH depletion showing its pro-apoptotic effect dependent on ROS overproduction. The treatment did not show a significant effect on normal cells—melanocytes—which indicates its high selectivity. The results suggest a possible benefit from the use of the ketoprofen and ultraviolet A irradiation as a new concept of melanotic melanoma therapy.
Highlights
IntroductionMalignant melanoma (malignum melanoma) is a tumor that originates from melanotic cells derived from neuroectodermal cells [1]
Malignant melanoma is a tumor that originates from melanotic cells derived from neuroectodermal cells [1]
In contrast to COLO829 melanoma cells, a significant reduction in the number of HEMn-DP cells was noted only for cells pre-treated with KTP at a concentration of 1.0 mM and irradiated with UVA radiation (UVAR), showing KTP and UVAR combination as a selective in the mode of action against melanotic melanoma cells
Summary
Malignant melanoma (malignum melanoma) is a tumor that originates from melanotic cells derived from neuroectodermal cells [1]. Most cases of de novo melanoma derive from epidermal melanocytes and it causes up to 80% of deaths in the patient suffering from skin cancer [2]. Melanoma is a type of skin cancer characterised by the high mortality rate, and unsuccessful therapy, which does not give satisfactory effects; in the 4th stage of clinical advancement, therapy does not give sufficient effects—the average life expectancy is 6–10 months, and less than 10% of patients survive 5 years [3,4,5]. The increase in ROS levels may induce a therapeutically beneficial pro-apoptotic effect that can be used to support the treatment of neoplastic diseases, including malignant melanoma. Long-term oxidative stress in cancer cells caused by ROS-generating drugs or therapies may exhaust their antioxidant mechanisms, which, after exceeding the appropriate concentration of free radicals in cells, may lead to apoptosis. Phototherapy can be deliberated as one of the new melanoma treatment
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