Polyamine-depletion induces p27(Kip1) and enhances dexamethasone-induced G(1) arrest and apoptosis in human T lymphoblastic leukemia cells

Glucocorticoid-induced apoptosis is preceded by G(1) arrest and supposed to be up-regulated by polyamine-depletion, which also induces G(1) arrest. In CEM leukemia cells, dexamethasone showed an antileukemic effect by inducin g G(1) arrest and apoptosis. DFMO, which depleted cellular polyamines by in hibiting ornithine decarboxylase, induced G(1) arrest but without apoptosis , though it enhanced dexamethasone-induced G(1) arrest and apoptosis. The G (1) arrest was associated with hypophosphorylation of pRb. Dexamethasone in hibited the increase of mutated p53 expression but had little effect on p21 (Waf1/Cip1) expression. The p27(Kip1) level was increased by dexamethasone or/and DFMO in line with the kinetics of G(1) arrest. Therefore, the up-reg ulation of dexamethasone-induced apoptosis by polyamine-depletion may be as sociated with additive down-regulation of G(1) progression via the p27(Kip1 )-pRb pathway. (C) 2000 Elsevier Science Ltd. All rights reserved.