Association of Dexamethasone-induced Apoptosis and G<SUB>1</SUB>-Arrest of Human Leukemic CEM Cells with Polyamine Deficit

Association of Dexamethasone-induced Apoptosis and G<SUB>1</SUB>-Arrest of Human Leukemic CEM Cells with Polyamine Deficit

<P> The effects of DFMO or/and putrescine on the dexamethasone-induced apoptosis of CEM cells were studied to investigate the role of polyamines in anti-leukemic glucocorticoid action. Dexamethasone- induced apoptosis was preceded by significant decreases of cellular polyamine contents and putrescine uptake activity. But DFMO produced decreases of putrescine and spermidine contents and marked increase of putrescine uptake activity, but did not induce apoptosis. However, dexamethasone and DFMO, respectively, induced G<SUB>1</SUB>-arrest in cell cycle and hypophosphorylation of pRb, resulting in the increase of G<SUB>1</SUB> to S ratio and decrease of CEM cell count. DFMO enhanced the dexamethasone-induced apoptosis and G<SUB>1</SUB>-arrest. On the other hand, putrescine little affected the apoptotic and G<SUB>1</SUB>-arresting activities of dexamethasone, but almost suppress the effects of DFMO and also the DFMO-dependent enhancement of dexamethasone effects. These results suggested that the dexamethasone-induced apoptosis to be associated with pRb hypophosphorylation and G<SUB>1</SUB>-arrest in CEM cells might be ascribed to the concomitant decreases of cellular polyamine contents and putrescine uptake activity.