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

Abstract

PURPOSE:

We hypothesized that vitamin D decreases rates of adenosine formation in human cutaneous melanoma cells through the inhibition of extracellular adenosine 5'-triphosphate breakdown, thereby affecting tumor cell viability. Therefore, the objective of this study was to explore the mechanisms of action of 1α, 25-dihydroxyvitamin D3 (1,25(OH)2 D3) on the activity and expression of ectonucleotidases in cutaneous melanoma cells.

METHODS:

A human melanoma cell line, SK-Mel-28, was treated with 1 to 50 nM of the active vitamin D metabolite (1,25(OH)2 D3) over 24 hours, followed by determination of NTPDase1/CD39 and ecto-5'-nucleotidase/CD73 activity and expression rates of the purinergic system-related NTPDASE1, NT5E and adenosine deaminase and vitamin D receptor. An 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay was used to evaluate cellular viability.

RESULTS:

1,25(OH)2 D3 decreased adenosine monophosphate hydrolysis via ecto-5'-nucleotidase/CD73 and expression of CD73, but did not change NTPDase1/CD39 activity; it increased the CD39 expression. We also observed an increase of cell viability at 1 nM, but this viability decreased as the concentrations of vitamin D active metabolite increased to 50 nM. There were no differences in gene expression levels.

CONCLUSION:

To the best of our knowledge, we showed for the first time a mechanism of control of adenosine production via modulation of the purinergic system in cutaneous melanoma cells treated with the active metabolite of vitamin D. This study provides original information regarding mechanisms, in which vitamin D plays a key role in preventing tumor progression in human melanoma cells.

• Authors: Margarete Dulce Bagatini, Kalyne Bertolin, Alessandra Bridi, Luana Paula Pelinson, Beatriz da Silva Rosa Bonadiman, Michele Mainardi Pillat, Paulo Bayard Dias Gonçalves, Henning Ulrich, Maria Rosa Chitolina Schetinger, Vera Maria Morsch
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 120 Issue 6 Pg. 9992-10000 (06 2019) ISSN: 1097-4644 [Electronic] United States
• PMID: 30548323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• GPI-Linked Proteins
• Neoplasm Proteins
• 5'-Nucleotidase
• NT5E protein, human
• Calcitriol

Topics

• 5'-Nucleotidase (biosynthesis, genetics)
• Calcitriol (pharmacology)
• Cell Line, Tumor
• GPI-Linked Proteins (biosynthesis, genetics)
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Melanoma (enzymology, genetics, pathology)
• Neoplasm Proteins (biosynthesis, genetics)
• Skin Neoplasms (enzymology, genetics, pathology)