Mechanisms of resistance to vitamin D action in human cancer cells

Abstract

El pdf es la versión post-print.Initial clinical trials in cancer patients with vitamin D compounds have shown acceptable toxicity but low activity. A number of mechanisms responsible for resistance to their action in cancer cells have been recently reported. They include reduced intracellular availability of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D], loss of vitamin D receptor (VDR) expression and deregulation of transcription corepressors that modulate VDR action. Here, we summarize the data in the literature on the altered activity of the enzymes (CYP27B1, CYP24A1) that controls 1,25(OH)2D levels, the repression of VDR by the transcription factor Snail1 and the overexpression of several VDR corepressors (NCoR, SMRT) in cancer cells. A better understanding of these processes must contribute to improved protocols for the clinical use of vitamin D compounds.The work in authors’ laboratory is supported by the Ministerio de Ciencia e Innovación of Spain, Comunidad de Madrid and European Union.Peer Reviewe