皮肤黑色素瘤（CM）由于其侵袭性且对常规治疗的反应通常有限，给治疗带来了挑战。探索新的治疗靶点至关重要，天然化合物已成为潜在的候选者。本研究旨在阐明姜黄素（一种以其抗炎、抗氧化和抗肿瘤特性而闻名的天然化合物）对转移性黑色素瘤细胞的影响，重点关注嘌呤能系统和免疫反应。将人黑色素瘤细胞系 SK-Mel-28 暴露于不同姜黄素浓度 6 或 24 小时，然后我们评估与嘌呤能系统和炎症级联相关的成分。使用 RT-qPCR，我们评估了 CD39 和 CD73 核酸外切酶以及腺苷脱氨酶 (ADA) 的基因表达。姜黄素有效下调 CD39、CD73 和 ADA 基因表达。流式细胞术分析表明，姜黄素在特定浓度下显着降低 CD39 和 CD73 蛋白表达。此外，A2A 受体的蛋白质表达在所有浓度下均有所下降。酶活性测定表明，姜黄素可调节 CD39、CD73 和 ADA 活性，其效果取决于浓度和治疗持续时间。姜黄素处理 24 小时后，细胞外 ATP 水平增加，强调了其调节水解活性的作用。姜黄素还通过降低 NLRP3 基因表达和影响关键炎症细胞因子的水平来显示抗炎特性。总之，本研究揭示了姜黄素作为 CM 治疗有前景的佐剂的潜力。姜黄素可调节嘌呤能系统关键成分的表达和活性，并具有抗炎作用，表明其在对抗 CM 方面具有潜在的治疗作用。这些发现强调了姜黄素的前景，并值得在黑色素瘤治疗的临床前和临床环境中进行进一步研究。© 2024。作者获得 Springer Nature B.V. 的独家许可。

Cutaneous melanoma (CM) poses a therapeutic challenge due to its aggressive nature and often limited response to conventional treatments. Exploring novel therapeutic targets is essential, and natural compounds have emerged as potential candidates. This study aimed to elucidate the impact of curcumin, a natural compound known for its anti-inflammatory, antioxidant, and anti-tumor properties, on metastatic melanoma cells, focusing on the purinergic system and immune responses. Human melanoma cell line SK-Mel-28 were exposed to different curcumin concentrations for either 6 or 24 h, after which we assessed components related to the purinergic system and the inflammatory cascade. Using RT-qPCR, we assessed the gene expression of CD39 and CD73 ectonucleotidases, as well as adenosine deaminase (ADA). Curcumin effectively downregulated CD39, CD73, and ADA gene expression. Flow cytometry analysis revealed that curcumin significantly reduced CD39 and CD73 protein expression at specific concentrations. Moreover, the A2A receptor's protein expression decreased across all concentrations. Enzymatic activity assays demonstrated that curcumin modulated CD39, CD73, and ADA activities, with effects dependent on concentration and duration of treatment. Extracellular ATP levels increased after 24 h of curcumin treatment, emphasizing its role in modulating hydrolytic activity. Curcumin also displayed anti-inflammatory properties by reducing NLRP3 gene expression and impacting the levels of key inflammatory cytokines. In conclusion, this study unveils the potential of curcumin as a promising adjuvant in CM treatment. Curcumin modulates the expression and activity of crucial components of the purinergic system and exhibits anti-inflammatory effects, indicating its potential therapeutic role in combating CM. These findings underscore curcumin's promise and warrant further investigation in preclinical and clinical settings for melanoma management.© 2024. The Author(s), under exclusive licence to Springer Nature B.V.