RT Journal Article SR Electronic T1 Mechanisms of Vitamin D-mediated Growth Inhibition in Prostate Cancer Cells: Inhibition of the Prostaglandin Pathway JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2525 OP 2530 VO 26 IS 4A A1 JACQUELINE MORENO A1 ARUNA V. KRISHNAN A1 DONNA M. PEEHL A1 DAVID FELDMAN YR 2006 UL http://ar.iiarjournals.org/content/26/4A/2525.abstract AB Calcitriol (1,25-dihydroxyvitamin D3), the active form of vitamin D, promotes growth inhibition and differentiation in prostate cancer (PCa) cells. To unravel the molecular pathways of calcitriol actions, cDNA microarray analysis was used to identify novel calcitriol target genes including two that play key roles in the metabolism of prostaglandins (PGs), known stimulators of PCa growth and progression. Calcitriol significantly decreases the expression of the PG synthesizing cyclooxygenase-2 (COX-2) gene, while increasing that of PG inactivating 15-prostaglandin dehydrogenase (15-PGDH). Calcitriol also inhibits the expression of the PG receptors EP2 and FP. It reduces the levels of biologically active PGs and inhibits PG actions in PCa cells, thereby decreasing the proliferative stimulus of PGs. We postulate that the regulation of the PG pathway contributes to the growth inhibitory actions of calcitriol. We also propose that calcitriol can be combined with non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit COX enzyme activity, as a potential therapeutic strategy in PCa. Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved