Antiproliferative Properties of the Serotonin Receptor Antagonist Ondansetron Correlate with Increased Nitric Oxides Release and Inducible Nitric Oxide Synthase Activity in the Acute Lymphoblastic Leukemia Cell Line REH

Abstract

A recent report from our group described that the (serotonin receptor-3)-antagonist ondansetron exhibits antiproliferative effects in the B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell line REH. Furthermore, after each application of ondansetron to cultured REH cells, significant increases (+23%) in the concentration of nitric oxides (NO) were observed in the cell supernatants after 72 hours incubation in standard conditions, and this effect was found to correlate with the described antiproliferative activity. This feature was further confirmed by using mRNA dot blot hybridizations with a specific gene probe for the inducible NO-synthase (iNOS), yielding significant increases (+100%) of iNOS mRNA, which were found to widely correlate with the detected increases of NO release, and also with the previously described antiproliferative effects. The presented results are the first report on high specific pro-inflammatory features of a (serotonin receptor 3)-antagonist in a BCP-ALL cell line, which are associated with previously described antiproliferative properties.