BRAF inhibitor candidate molecule usnic acid might use both intrinsic and extrinsic pathways of apoptosis

Résumé

Background/aim: Melanoma is one of the most aggressive cancers and treatment methods commonly used for patients with skin cancer include checkpoint and BRAF/MEK inhibitors, traditional chemotherapy drugs, radiation and adjuvant treatment methods. Due to the resistance and toxic effects that the patient develops against the drugs, an effective treatment method has not been developed for melanoma yet. Materials and methods: In this study we evaluated the anti-cancer effect of usnic acid (UA) on A-375 melanoma cells and human epidermal melanocytes by xCELLigence real-time cell analysis system. To determine through which cell death pathway UA exerts its anti-proliferative effect, its apoptotic effect potential was investigated. Caspase-3 and Caspase-9 enzyme assays and the expression analysis of 84 genes from apoptosis pathway were carried out in UA treated and non-treated A-375 cells.Results: It was found that UA has an anti-proliferative effect on A-375 cells and does not have a cytotoxic effect on human epidermal melanocytes. UA treatment led to statistically significant increases in both Caspase-3 and Caspase-9 enzyme activities. Moreover, the expression levels of 61 genes (mainly pro-apoptotic genes) were increased however the expression levels of 23 genes (mainly anti-apoptotic genes) were decreased in response to UA treatment. It was found that this effect might be developed through both the extrinsic and intrinsic apoptosis pathways however the extrinsic pathway was more pronounced.Conclusion: As a result of the obtained findings herein, it could be concluded that UA might be a promising candidate drug molecule for the melanoma treatment for the future through topical application or encapsulation with nanocarriers.