Investigation of the apoptotic effect of vulpinic acid on the melanoma cancer cell

Skin cancer is a type of cancer that affects the skin. Melanoma, is the most harmful type of skin cancer, causes 4% of deaths in the world. The scientific world, which closely follows the discovery of antibiotics and their fundamental contribution to human health, is in search of new active substances with activity against pathogenic microbes. Lichens have been the subject of these pioneering studies. Among the lichen active substances, usnic acid has attracted the attention of many scientists and is considered as a special lichen secondary metabolite. In this thesis, it was aimed to evaluate the effects of usnic acid, one of the secondary metabolites of lichen, on the apoptosis pathway by using human melanocyte cell line (NHEM-Ad) and malignant melanoma cell line (A-375), and to investigate its use in cancer treatment in vitro with various molecular and biochemical approaches. The antiproliferative effect of usnic acid on normal human melanocyte cell line and malignant melanoma cell line was determined by xCELLigence real-time cell analysis system. In the light of the data obtained, the IC50 value was calculated as 3.47 μM for the human melanocyte cell line (NHEM-Ad) and 20 μM for the malignant melanoma cell line (A-375). The varying expression profiles of 84 genes related to apoptosis between the control and treatment groups and the results obtained from Caspase-3 and Caspase-9 enzyme activity tests showed that usnic acid can exhibit anti-cancer effects by inducing apoptosis in human malignant melanoma cell line. It was found that this effect developed through both the extrinsic and intrinsic pathways of apoptosis, but when we evaluated it according to the mRNA profile, the extrinsic pathway was more dominant. It is thought that the results obtained from this study indicate that usnic acid can be used as a drug candidate molecule in the treatment of skin cancer. We hope that the findings obtained will be an important resource for other researchers. We believe that the use of usnic acid as a drug in the form of topical or transdermal applications may have significant potential in the treatment of skin cancer in the future.