Polyamine-depletion induces p27Kip1 and enhances dexamethasone-induced G1 arrest and apoptosis in human T lymphoblastic leukemia cells.
Glucocorticoid-induced apoptosis is preceded by G1 arrest and supposed to be up-regulated by polyamine-depletion, which also induces G1, arrest. In CEM leukemia cells, dexamethasone showed an antileukemic effect by inducing G1 arrest and apoptosis. DFMO, which depleted cellular polyamines by inhibiting ornithine decarboxylase, induced G1 arrest but without apoptosis, though it enhanced dexamethasone-induced G1 arrest and apoptosis. The G1 arrest was associated with hypophosphorylation of pRb. Dexamethasone inhibited the increase of mutated p53 expression but had little effect on p2Wafl/Cip1 expression. The p27Kip1, level was increased by dexamethasone or and DFMO in line with the kinetics of G1 arrest. Therefore, the up-regulation of dexamethasone-induced apoptosis by polyamine-depletion may be associated with additive down-regulation of G1 progression via the p27Kip1-pRb pathtway.
Choi
S H
SH
Department of Pharmacology, Korea University College of Medicine, Seoul, South Korea.
Kim
S W
SW
Choi
D H
DH
Min
B H
BH
Chun
B G
BG
D017209:Apoptosis / Q000187:drug effects*; D015317:Biogenic Polyamines / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002455:Cell Division; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003907:Dexamethasone / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D015458:Leukemia, T-Cell / Q000378:metabolism / Q000473:pathology*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D015317:Biogenic Polyamines; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003907:Dexamethasone