title: Effect of NSAIDs on the aminopeptidase activity of cultured human osteoblasts.
abstract: Aminopeptidases (APs) are involved in various physiological and pathological processes. In tumor tissues the expression of APs, cyclooxygenase-2 and its metabolites are increased. The objective was to determine the effect of certain NSAIDs on the AP activity of osteoblasts. Primary cultures of osteoblast were treated with different concentrations of indomethacin, meloxicam, naproxen, nimesulide, and piroxicam. The AP activity was fluorimetrically determined using aminoacyl-β-naphthylamides (aa-βNAs) as substrates: Ala-βNA, Arg-βNA, Gly-βNA, Leu-βNA, Lys-βNA, Met-βNA, and Phe-βNA. The five NSAIDs showed an inhibitory effect of AP activity against the study substrates depending on the dose tested. Meloxicam and piroxicam had the highest inhibitory effect on enzymatic activity, with an IC50 of around 70 μM. Our results suggest that the physiological alteration of osteoblasts in the presence of NSAIDs may be a consequence of AP inhibition, suggesting a potential clinical role for these drugs against cancer in combination with chemotherapeutic agents.
authors.affiliation: Biobanco, Sistema Sanitario Público de Andalucía, Junta de Andalucía, Granada, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Lucena
authors.affiliation: Biomedical Group (BIO277), Department of Stomatology, School of Dentistry, University of Granada. Instituto Investigación Biosanitaria, ibs.Granada, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Reyes-Botella
authors.affiliation: Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences. University of Granada. Instituto Investigación Biosanitaria, ibs.Granada, Spain.
authors.forename: O
authors.initials: O
authors.lastname: García-Martínez
authors.affiliation: Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences. University of Granada. Instituto Investigación Biosanitaria, ibs.Granada, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Ramos-Torrecillas
authors.affiliation: Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences. University of Granada. Instituto Investigación Biosanitaria, ibs.Granada, Spain.
authors.forename: E
authors.initials: E
authors.lastname: De Luna Bertos
authors.affiliation: Biomedical Group (BIO277), Department of Nursing, Faculty of Health Sciences. University of Granada. Instituto Investigación Biosanitaria, ibs.Granada, Spain; Institute of Neuroscience, Parque Tecnológico Ciencias de la Salud, Armilla, Granada, University of Granada, Spain. Electronic address: crr@ugr.es.
authors.forename: C
authors.initials: C
authors.lastname: Ruiz
mesh_terms: D000328:Adult; D000626:Aminopeptidases / Q000378:metabolism*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000626:Aminopeptidases
keywords: AminoPeptidase; NSAIDs; Osteoblasts