1 alpha,25-Dihydroxyvitamin D-3 exerts tissue-specific effects on estrogen and androgen metabolism
Lundqvist, Johan; Norlin, Maria; Wikvall, Kjell
It is well-known that 1 alpha,25-dihydroxyvitamin D-3 and analogs exert anti-proliferative and pro-differentiating effects and these compounds have therefore been proposed to be of potential use as anti-cancer agents. Due to its effects on aromatase gene expression and enzyme activity, 1 alpha,25-dihydroxyvitamin D-3 has been proposed as an interesting substance in breast cancer treatment and prevention. In the present study, we have examined the effects of 1 alpha,25-dihydroxyvitamin D-3 on estrogen and androgen metabolism in adrenocortical NCI-H295R cells, breast cancer MCF-7 cells and prostate cancer LNCaP cells. The NCI-H295R cell line has been proposed as a screening tool to study endocrine disruptors. We therefore studied whether this cell line reacted to 1 alpha,25-dihydroxyvitamin D-3 treatment in the same way as cells from important endocrine target tissues. 1 alpha,25-Dihydroxyvitamin D-3 exerted cell line-specific effects on estrogen and androgen metabolism. In breast cancer MCF-7 cells, aromatase gene expression and estradiol production were decreased, while production of androgens was markedly increased. In NCI-H295R cells, 1 alpha,25-dihydroxyvitamin D-3 stimulated aromatase expression and decreased dihydrotestosterone production. In prostate cancer LNCaP cells, aromatase expression increased after the same treatment, as did production of testosterone and dihydrotestosterone. In summary, our data show that 1 alpha,25-dihydroxyvitamin D-3 exerts tissue-specific effects on estrogen and androgen production and metabolism. This is important knowledge about 1 alpha,25-dihydroxyvitamin D-3 as an interesting substance for further research in the field of breast cancer prevention and treatment. Furthermore, the observed cell line-specific effects are of importance in the discussion about NCI-H295R cells as a model for effects on estrogen and androgen metabolism.. (C) 2011 Elsevier B.V. All rights reserved.
17 beta-HSD, 17 beta-hydroxysteroid dehydrogenase; ELISA, enzyme-linked immunosorbent assay; SAM, selective aromatase modulator; TBP, TATA box binding protein; VDR, vitamin D receptor
Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids
2011, Volym: 1811, nummer: 4, sidor: 263-270
Pharmacology and Toxicology
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