Pharmacological melatonin induces mitochondrial dysfunction and alters extracellular nucleotide metabolism and CD39/CD73 expression in human melanoma cells.
5 affiliations
- 1Post-Graduate Program in Health Sciences, Community University of the Region of Chapecó (UNOCHAPECÓ), Chapecó, SC, 89809-900, Brazil.
- 2Postgraduate Program in Biochemistry, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil.
- 3Multicenter Postgraduate Program in Biochemistry and Molecular Biology, State University of Santa Catarina (UDESC), Lages, Brazil.
- 4Post-Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, Brazil.
- 5Post-Graduate Program in Health Sciences, Community University of the Region of Chapecó (UNOCHAPECÓ), Chapecó, SC, 89809-900, Brazil. [email protected].
Abstract
Cutaneous melanoma remains an aggressive malignant neoplasm characterized by molecular heterogeneity and therapeutic resistance, highlighting the need to identify alternative pathways involved in tumor progression. Purinergic signaling, particularly the conversion of extracellular ATP to immunosuppressive adenosine mediated by ectonucleotidases CD39 (NTPDase1) and CD73 (ecto-5'-nucleotidase), has emerged as a critical determinant of melanoma biology, but its potential regulation by melatonin remains unexplored.Here, we investigated whether pharmacological melatonin (0.1-5 mM, 24 and 48 h) influences metabolic activity, mitochondrial homeostasis, and extracellular nucleotide metabolism in two human melanoma cell lines with distinct molecular profiles (SK-MEL-28 and A375). Melatonin reduced metabolic activity and induced mitochondrial depolarization in both cell lines, although A375 cells exhibited greater mitochondrial sensitivity than SK-MEL-28 cells. These mitochondrial alterations were accompanied by distinct apoptosis- and inflammation-related transcriptional responses, indicating lineage-dependent cellular response to pharmacological melatonin. In parallel, melatonin differentially altered extracellular nucleotide metabolism and CD39/CD73 gene expression, with distinct responses observed between the two melanoma cell lines. Collectively, these findings indicate that the biological effects of pharmacological melatonin extend beyond mitochondrial dysfunction and involve remodeling of extracellular nucleotide metabolism, providing new evidence for an interaction between melatonergic and purinergic signaling in melanoma.
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BibTeX
@article{ozelame2026pharmacological,
title = {{Pharmacological melatonin induces mitochondrial dysfunction and alters extracellular nucleotide metabolism and CD39/CD73 expression in human melanoma cells.}},
author = {Bruna Cristina Ozelame and Daiane Mânica and Gilnei Bruno da Silva and Andreia Machado Cardoso and Margarete Dulce Bagatini and Aline Mânica},
journal = {Purinergic signalling},
year = {2026},
month = oct,
doi = {10.1007/s11302-026-10193-z},
url = {https://europepmc.org/article/MED/42900413},
note = {CC BY},
}
RIS
TY - JOUR
TI - Pharmacological melatonin induces mitochondrial dysfunction and alters extracellular nucleotide metabolism and CD39/CD73 expression in human melanoma cells.
AU - Bruna Cristina Ozelame
AU - Daiane Mânica
AU - Gilnei Bruno da Silva
AU - Andreia Machado Cardoso
AU - Margarete Dulce Bagatini
AU - Aline Mânica
PY - 2026
DA - 2026/10/20
JO - Purinergic signalling
DO - 10.1007/s11302-026-10193-z
UR - https://europepmc.org/article/MED/42900413
AB - Cutaneous melanoma remains an aggressive malignant neoplasm characterized by molecular heterogeneity and therapeutic resistance, highlighting the need to identify alternative pathways involved in tumor progression. Purinergic signaling, particularly the conversion of extracellular ATP to immunosuppressive adenosine mediated by ectonucleotidases CD39 (NTPDase1) and CD73 (ecto-5'-nucleotidase), has emerged as a critical determinant of melanoma biology, but its potential regulation by melatonin remains unexplored.Here, we investigated whether pharmacological melatonin (0.1-5 mM, 24 and 48 h) influences metabolic activity, mitochondrial homeostasis, and extracellular nucleotide metabolism in two human melanoma cell lines with distinct molecular profiles (SK-MEL-28 and A375). Melatonin reduced metabolic activity and induced mitochondrial depolarization in both cell lines, although A375 cells exhibited greater mitochondrial sensitivity than SK-MEL-28 cells. These mitochondrial alterations were accompanied by distinct apoptosis- and inflammation-related transcriptional responses, indicating lineage-dependent cellular response to pharmacological melatonin. In parallel, melatonin differentially altered extracellular nucleotide metabolism and CD39/CD73 gene expression, with distinct responses observed between the two melanoma cell lines. Collectively, these findings indicate that the biological effects of pharmacological melatonin extend beyond mitochondrial dysfunction and involve remodeling of extracellular nucleotide metabolism, providing new evidence for an interaction between melatonergic and purinergic signaling in melanoma.
SN - 1573-9538
SN - 1573-9546
ER -