Regulation of Prostaglandin Metabolism by Calcitriol Attenuates Growth Stimulation in Prostate Cancer Cells

• DOI: 10.1158/0008-5472.can-05-1435
• Publication Date: 2017-07-21T22:27:13Z
• Authors: Jacqueline Moreno; Aruna V. Krishnan; Srilatha Swami; Larisa Nonn; Donna M. Peehl; David Feldman
• Keywords: Male; Neoplasms, Hormone-Dependent; Anti-Inflammatory Agents, Non-Steroidal; Receptors, Prostaglandin; Genes, fos; Membrane Proteins; Prostatic Neoplasms; Drug Synergism; Cell Growth Processes; Dinoprostone; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; 0302 clinical medicine; Calcitriol; Cyclooxygenase 2; Prostaglandin-Endoperoxide Synthases; Hydroxyprostaglandin Dehydrogenases; Prostaglandins; Humans; RNA, Messenger

Abstract Calcitriol exhibits antiproliferative and prodifferentiation effects in prostate cancer. Our goal is to further define the mechanisms underlying these actions. We studied established human cancer cell lines primary prostatic epithelial cells showed that calcitriol regulated expression of genes involved metabolism prostaglandins (PGs), known stimulators growth. significantly repressed mRNA protein prostaglandin endoperoxide synthase/cyclooxygenase-2 (COX-2), key PG synthesis enzyme. also up-regulated 15-hydroxyprostaglandin dehydrogenase, enzyme initiating catabolism. This dual action was associated with decreased E2 secretion into conditioned media exposed calcitriol. receptors EP2 FP, providing a potential additional mechanism suppression biological activity PGs. treatment attenuated PG-mediated functional responses, including stimulation The combination nonsteroidal anti-inflammatory drugs (NSAIDs) synergistically acted achieve significant growth inhibition at ∼2 10 times lower concentrations than when used alone. In conclusion, regulation actions constitutes novel pathway may contribute its cells. propose nonselective NSAIDs might be useful chemopreventive and/or therapeutic strategy men cancer, as it would allow use both drugs, thereby reducing their toxic side effects.