1α, 25-Dihydroxyvitamin D3 alters ectonucleotidase expression and activity in human cutaneous melanoma cells

Margarete Dulce Bagatini1,2, Kalyne Bertolin3, Alessandra Bridi3

  • 1Department of Biochemistry and Molecular Biology, Academic Coordination, Campus Chapecó, Federal University of Fronteira Sul, Chapecó, SC, Brazil.

Abstract

Insights

Vitamin D metabolite 1,25(OH)2D3 affects adenosine production in melanoma cells by modulating the purinergic system. This study reveals a novel mechanism for vitamin D in controlling tumor progression in cutaneous melanoma.

Area of Science:

  • * Oncology
  • * Dermatology
  • * Molecular Biology

Background:

  • * Adenosine plays a critical role in tumor cell viability and progression.
  • * The purinergic system, involving ectonucleotidases, regulates extracellular adenosine levels.
  • * Vitamin D's role in melanoma is under investigation, particularly its impact on adenosine metabolism.

Purpose of the Study:

  • * To investigate the mechanism by which 1α, 25-dihydroxyvitamin D3 (1,25(OH)2D3) influences ectonucleotidase activity and expression in human cutaneous melanoma cells.
  • * To determine the effect of 1,25(OH)2D3 on adenosine formation and its subsequent impact on melanoma cell viability.
  • * To explore the modulation of the purinergic system by vitamin D in the context of melanoma.

Main Methods:

  • * Treatment of human melanoma cell line (SK-Mel-28) with varying concentrations of 1,25(OH)2D3 (1-50 nM) for 24 hours.
  • * Assay of ectonucleotidase activities (NTPDase1/CD39, ecto-5'-nucleotidase/CD73) and expression.
  • * Evaluation of cellular viability using the MTT assay and assessment of gene expression levels.

Main Results:

  • * 1,25(OH)2D3 decreased adenosine monophosphate hydrolysis via ecto-5'-nucleotidase/CD73 and reduced CD73 expression.
  • * NTPDase1/CD39 activity remained unchanged, while its expression increased with 1,25(OH)2D3 treatment.
  • * Cell viability initially increased at 1 nM 1,25(OH)2D3 but decreased at higher concentrations (50 nM).

Conclusions:

  • * This study demonstrates a novel mechanism for vitamin D in controlling adenosine production in melanoma cells through purinergic system modulation.
  • * The findings suggest that vitamin D plays a significant role in regulating tumor progression in human cutaneous melanoma.
  • * 1,25(OH)2D3 impacts ecto-5'-nucleotidase/CD73 and CD39 expression, influencing the tumor microenvironment.

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