Effects of dexamethasone and aminophylline on survival of Jurkat and HL-60 cells.
The effects of dexamethasone and aminophylline on survival of Jurkat T-lymphocytic leukemia cells and HL-60 promyelocytic leukemia cells were investigated. Dexamethasone (10, 1000 nM) and aminophylline (1, 100 microM) induced apoptosis in Jurkat and HL-60 cells in a concentration-dependent manner. Treatment with a combination of dexamethasone (10 nM) and aminophylline (1 microM) significantly increased the number of apoptotic HL-60 cells, but not that of Jurkat cells, compared with dexamethasone (10 nM) or aminophylline (1 microM) treatment alone. Dexamethasone and aminophylline also increased the number of phospho-histone H2B (Ser(14))-positive Jurkat and HL-60 cells. Phospho-histone H2B (pH2B)-positive HL-60 cells were significantly increased by treatment with a combination of dexamethasone (10 nM) and aminophylline (1 microM), although no such effect was observed in Jurkat cells. On the other hand, simultaneous treatment with 10 nM dexamethasone and 1 muM aminophylline activated the 36-kDa MBP kinase, pro-apoptotic protein kinase in HL-60 cells. The activation of 36-kDa MBP kinase by dexamethasone and aminophylline was supported by studies showing an increase in the number of pH2B-positive and apoptotic Jurkat and HL-60 cells upon exposure to these drugs. Thus treatment with a combination of dexamethasone and aminophylline accelerates apoptosis of HL-60 cells via activation of 36-kDa MBP kinase and H2B phosphorylation.
Kizawa
Yasuo
Y
Department of Physiology and Anatomy, Nihon University College of Pharmacy, Funabashi, Chiba 275-8555, Japan.
Furuya
Minori
M
Saito
Kiyoshige
K
Masuko
Takashi
T
Kusama
Tadashi
T
D000628:Aminophylline / Q000008:administration & dosage / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018922:HL-60 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000099317:Hippo Kinases
D000628:Aminophylline; D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C095566:STK4 protein, human; D000099317:Hippo Kinases