Deguelin represses both the expression of nucleophosmin and some nucleoporins: Nup88 and Nup214 in Jurkat cells

Abstract

Since the first report about cytoplasmic nucleophosmin (NPM) in acute myelogenous leukemia with a normal karyotype was announced, the shuttling activity of NPM and its proper subcellular localization have drawn many attentions. Mechanisms that regulate nucleocytoplasmic transport of proteins may provide novel opportunities for drug development. Here we show that, in Jurkat cells, strong fluorescence density of NPM prevails in the nucleus, while, some key nucleoporins: Nup88 and Nup214 localize mainly in the cytoplasm. Deguelin, a natural occurring rotenoid, presents powerful anti-leukemia effects through proliferation inhibition and apoptosis induction in Jurkat cells. Deguelin downregulates the expression of NPM, Nup88 and Nup214 in a dose-dependent manner and reverts the localization of Nup88 and Nup214 to nuclear rim. These results suggest that deguelin exhibit its strong anti-leukemia effects might through the regulation of some nucleoporins, thus influence the subsequent abnormal expressions or localizations of some key proteins involved in proliferation and/or apoptosis, such as: NPM. © 2008 Pharmaceutical Society of Japan.