da Silva Gilnei B, Manica Daiane, Dallagnol Paula, Narzetti Rafael A, Marafon Filomena, da Silva Alana P, de S Matias Letícia, Cassol Joana V, Moreno Marcelo, Kempka Aniela P, Bagatini Margarete D
Multicentric Postgraduate Program in Biochemistry and Molecular Biology, State University of Santa Catarina, Lages, SC, Brazil.
Postgraduate Program in Biochemistry, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
Purinergic Signal. 2025 Apr;21(2):353-363. doi: 10.1007/s11302-024-10040-z. Epub 2024 Jul 20.
Cancer cases have increased worldwide. Cutaneous melanoma (CM), a highly metastatic skin cancer, largely contributes to global statistical cancer death data. Research has shown that rosmarinic acid (RA) is a promising phenolic compound with antineoplastic properties. Thus, we investigated the effects of RA on apoptosis-inducing in melanoma cells, purinergic signaling modulation, and cytokine levels. We treated SK-MEL-28 cells for 24 h with different concentrations of RA and assessed the apoptosis, CD39, CD73, and A2A expression, and cytokine levels. We found RA-induced apoptosis in melanoma cells. Regarding the purinergic system, we verified that RA downregulated the expression of CD73 and A2A, specially at high concentrations of treatment. Additionally, RA increased IL-6, IL-4, IL-10, IFN-γ, and TNF-α levels. Our in vitro results confirm RA's potential to be used to induce melanoma cell apoptosis, having CD73 and A2A as targets when reversion of immune suppression is desired. Further studies in animal models and clinical trials focusing on RA's modulation of purinergic signaling in melanoma are required.
全球癌症病例有所增加。皮肤黑色素瘤（CM）是一种具有高度转移性的皮肤癌，在很大程度上影响了全球癌症死亡统计数据。研究表明，迷迭香酸（RA）是一种具有抗肿瘤特性的有前景的酚类化合物。因此，我们研究了RA对黑色素瘤细胞诱导凋亡、嘌呤能信号调节和细胞因子水平的影响。我们用不同浓度的RA处理SK-MEL-28细胞24小时，并评估凋亡、CD39、CD73和A2A表达以及细胞因子水平。我们发现RA可诱导黑色素瘤细胞凋亡。关于嘌呤能系统，我们证实RA下调了CD73和A2A的表达，特别是在高浓度处理时。此外，RA增加了IL-6、IL-4、IL-10、IFN-γ和TNF-α的水平。我们的体外研究结果证实了RA在诱导黑色素瘤细胞凋亡方面的潜力，在需要逆转免疫抑制时，以CD73和A2A为靶点。需要在动物模型和临床试验中进一步研究RA对黑色素瘤中嘌呤能信号的调节作用。
