Effects of Dexamethasone and Aminophylline on Survival of Jurkat and HL-60 Cells

• Published in: Biological & Pharmaceutical Bulletin 2006, Vol.29(2), pp.281-285
• Main Authors: Kizawa, Yasuo, Furuya, Minori, Saito, Kiyoshige, Masuko, Takashi, Kusama, Tadashi
• Format: Article
• Language: English
• Subjects: aminophylline; Aminophylline - administration & dosage; Aminophylline - pharmacology; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; apoptosis; Apoptosis - drug effects; dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - pharmacology; Dose-Response Relationship, Drug; Drug Synergism; Histones - metabolism; HL-60; HL-60 Cells; Humans; Jurkat; Jurkat Cells; phospho-histone H2B; Protein-Serine-Threonine Kinases - metabolism
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.29.281

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 μM) induced apoptosis in Jurkat and HL-60 cells in a concentration-dependent manner. Treatment with a combination of dexamethasone (10 nM) and aminophylline (1 μM) significantly increased the number of apoptotic HL-60 cells, but not that of Jurkat cells, compared with dexamethasone (10 nM) or aminophylline (1 μM) treatment alone. Dexamethasone and aminophylline also increased the number of phospho-histone H2B (Ser14)-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 μM), although no such effect was observed in Jurkat cells. On the other hand, simultaneous treatment with 10 nM dexamethasone and 1 μM 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.