Vitamin D and Testosterone Co-ordinately Modulate Intracellular Zinc Levels and Energy Metabolism in Prostate Cancer Cells

Publication date: Available online 18 January 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Polly Zhang, Adam Schatz, Babatunde Adeyemi, David Kozminski, JoEllen Welsh, Martin Tenniswood, Wei-Lin Winnie WangAbstractVitamin D3 and its receptor are responsible for controlling energy expenditure in adipocytes and have direct roles in the transcriptional regulation of energy metabolic pathways. This phenomenon also has a significant impact on the etiology of prostate cancer (PCa). Using several in vitro models, the roles of vitamin D3 on energy metabolism and its implication in primary, early and late invasive PCa was investigated. BODIPY staining and qPCR analyses show that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) up-regulates de novo lipogenesis in PCa cells by orchestrating transcriptional regulation that affects cholesterol and lipid metabolic pathways. This lipogenic effect is highly dependent on the interaction of several nuclear receptors and their corresponding ligands, including androgen receptor (AR), vitamin D receptor (VDR), retinoid X receptor (RXR). In contrast, inhibition of peroxisome proliferator-activated receptor alpha (PPARĪ±) signaling blocks the induction of the lipogenic phenotype induced by these receptors. Furthermore, 1,25(OH)2D3, T and 9 cis-retinoic acid (9-cis RA) together redirect cytosolic citrate metabolism toward fatty acid synthesis by restoring normal prostatic zinc homeostasis that functions to truncate TCA cycle...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research