New signalling pathway involved in the anti-proliferative action of vitamin D₃ and its analogues in human neuroblastoma cells. A role for ceramide kinase

Neuropharmacology
Francesca BiniElisabetta Meacci

Abstract

1α,25-Dihydroxyvitamin D3 (1,25(OH)₂D₃), a crucial regulator of calcium/phosphorus homeostasis, has important physiological effects on growth and differentiation in a variety of malignant and non-malignant cells. Synthetic structural hormone analogues, with lower hypercalcemic side effects, are currently under clinical investigation. Sphingolipids appear to be crucial bioactive factors in the control of the cell fate: the phosphorylated forms, sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), are mitogenic factors, whereas sphingosine and ceramide (Cer) usually act as pro-apoptotic agents. Although many studies correlate S1P function to impaired cell growth, the relevance of C1P/Cer system and its involvement in neuroblastoma cells remain to be clarified. Here, we demonstrated the anti-proliferative effect of 1,25(OH)₂D₃ as well as of its structural analogues, ZK156979 and ZK191784, in human SH-SY5Y cells, as judged by [³H]thymidine incorporation, cell growth and evaluation of active ERK1/2 levels. The inhibition of ceramide kinase (CerK), the enzyme responsible for C1P synthesis, by specific gene silencing or pharmacological inhibition, drastically reduced cell proliferation. 1,25(OH)₂D₃ and ZK191784 treatment indu...Continue Reading

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Citations

Jun 28, 2014·Biomolecules·Anthony S DonTimothy A Couttas
Sep 4, 2014·Food & Function·Alessia FratiElisabetta Meacci
May 6, 2015·Toxins·Io-Guané RiveraAntonio Gomez-Muñoz
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Feb 16, 2013·Biochimica Et Biophysica Acta·Antonio Gomez-MuñozMiguel Trueba
Jan 28, 2017·British Journal of Pharmacology·Mercedes Garcia-GilElisabetta Meacci
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Jan 21, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Natalia PresaAntonio Gomez-Muñoz

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