Investigation of antitumoral potentials of some lichen-derived secondary metabolites on A375 melanoma cells

Melanoma is a type of skin cancer that originates from melanocyte cells and occurs primarily in the skin. While melanoma is seen only in the epidermis in its early stages, it is inevitable to see microinvasions that can extend to the superficial papillary dermis in later stages and metastases with invasion deep into the dermis in later stages. Since chemotherapy and radiotherapy methods used in the treatment of melonoma do not show enough benefit, the use of natural complementary and alternative products has become widespread. The most remarkable organism group used in these studies is lichens. Although antitumoural activity of secondary metabolites obtained from lichens has been shown in many cancer types, antitumoural activity against melanoma has not been investigated. In our study, A375 cell line, which is a melanoma cell line, was used and the anti-proliferative effect of diffractaic acid, evernic acid, vulpinic acid, stichtic acid and salazinic acid on A375 cells and their effects on metastatic, apoptotic and inflammatory markers were investigated. MTT test was performed to determine the anti-proliferative effects of the applied lichen secondary metabolites, as well as vascular endothelial growth factor (VEGF) level to determine the anti-metastatic effect and Caspase 3, 8 and 9 levels to examine the apoptotic effect, Interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β) and granulocyte macrophage colony-stimulating factor (GM-CSF) levels were measured using ELISA kit. The study was designed as five replicates. Analyses were performed using SPSS for Windows v16.0 package programme. ANOVA was used to test statistical differences between groups for all parameters and Tukey multiple comparison tests were used for subgroup comparisons. Mean±standard deviation values were given as descriptive statistics. The difference or relationship was considered statistically significant if p<0.05. Our findings showed that lichen secondary metabolites suppressed proliferation, inflammation, metastasis and angiogenesis of A375 cells and induced apoptosis. As a result of these results, supportive results were obtained that diffractaic acid, evernic acid, vulpinic acid, stictic acid and salazinic acid are promising theropathic agents and can be used in chemotherapy.