Polyamine-depletion induces p27Kip1 and enhances dexamethasone-induced G1 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 inducing G(1) arrest and apoptosis. DFMO, which depleted cellular polyamines by inhibiting 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 inhibited 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-regulation of dexamethasone-induced apoptosis by polyamine-depletion may be associated with additive down-regulation of G(1) progression via the p27(Kip1)-pRb pathway. (C) 2000 Elsevier Science Ltd. All rights reserved.