Curcumin modulates purinergic signaling and inflammatory response in cutaneous metastatic melanoma cells.

Autor: Manica D; Department of Biochemistry, Biochemistry Graduate Program, Federal University of Santa Catarina, Florianopolis, SC, Brazil., da Silva GB; Multicentric Graduate Program in Biochemistry and Molecular Biology, State University of Santa Catarina, Lages, SC, Brazil., Narzetti RA; Department of Biochemistry, Biochemistry Graduate Program, Federal University of Santa Catarina, Florianopolis, SC, Brazil., Dallagnoll P; Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapeco, SC, Brazil., da Silva AP; Department of Biochemistry, Biochemistry Graduate Program, Federal University of Santa Catarina, Florianopolis, SC, Brazil., Marafon F; Department of Biochemistry, Biochemistry Graduate Program, Federal University of Santa Catarina, Florianopolis, SC, Brazil., Cassol J; Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapeco, SC, Brazil., de Souza Matias L; Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapeco, SC, Brazil., Zamoner A; Department of Biochemistry, Biochemistry Graduate Program, Federal University of Santa Catarina, Florianopolis, SC, Brazil., de Oliveira Maciel SFV; Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapeco, SC, Brazil., Moreno M; Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapeco, SC, Brazil. marcelo.moreno@uffs.edu.br., Bagatini MD; Department of Biochemistry, Biochemistry Graduate Program, Federal University of Santa Catarina, Florianopolis, SC, Brazil. margaretebagatini@yahoo.com.br.; Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapeco, SC, Brazil. margaretebagatini@yahoo.com.br.
Jazyk: angličtina
Zdroj: Purinergic signalling [Purinergic Signal] 2024 May 27. Date of Electronic Publication: 2024 May 27.
DOI: 10.1007/s11302-024-10023-0
Abstrakt: 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.)
Databáze: MEDLINE
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