Rosmarinic acid modulates purinergic signaling and induces apoptosis in melanoma cells.

IF 3 4区 医学 Q2 NEUROSCIENCES Purinergic Signalling Pub Date : 2024-07-20 DOI:10.1007/s11302-024-10040-z
Gilnei B da Silva, Daiane Manica, Paula Dallagnol, Rafael A Narzetti, Filomena Marafon, Alana P da Silva, Letícia de S Matias, Joana V Cassol, Marcelo Moreno, Aniela P Kempka, Margarete D Bagatini
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Abstract

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.

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迷迭香酸可调节嘌呤能信号转导并诱导黑色素瘤细胞凋亡。
全球癌症病例不断增加。皮肤黑色素瘤(CM)是一种高度转移性皮肤癌,在全球癌症死亡统计数据中占很大比例。研究表明,迷迭香酸(RA)是一种具有抗肿瘤特性的酚类化合物。因此,我们研究了迷迭香酸对黑色素瘤细胞凋亡诱导、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,并评估细胞凋亡、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。在嘌呤能系统方面,我们证实 RA 下调了 CD73 和 A2A 的表达,尤其是在高浓度处理时。此外,RA 还能提高 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 具有诱导黑色素瘤细胞凋亡的潜力,当需要逆转免疫抑制时,可将 CD73 和 A2A 作为靶点。我们需要在动物模型和临床试验中进一步研究 RA 对黑色素瘤嘌呤能信号转导的调节作用。
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来源期刊
Purinergic Signalling
Purinergic Signalling 医学-神经科学
CiteScore
6.60
自引率
17.10%
发文量
75
审稿时长
6-12 weeks
期刊介绍: Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.
期刊最新文献
Correction to: Preparation and preliminary evaluation of a tritium-labeled allosteric P2X4 receptor antagonist. Machine learning-aided search for ligands of P2Y6 and other P2Y receptors. Purinergic regulation of pulmonary vascular tone. Role of ecto-5'-nucleotidase in bladder function activity and smooth muscle contractility. Unexpected role of microglia and P2Y12 in the induction of and emergence from anesthesia.
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