The role of Ca2+ and protein kinase C in the differentiation of HL-60 cells induced by 1 alpha,25(OH)2D3 and diltiazem.
The roles of calcium (Ca2+) and protein kinase C in the differentiation of HL-60 cells induced by 1 alpha,25(OH)2D3 (D3) and/or a Ca2+ antagonist, diltiazem(D-cis, L-cis), were elucidated. D3 and diltiazem (100 microM) inhibited cell proliferation, and diltiazem enhanced the D3-induced differentiation. There was no difference in potency between the two isomers of diltiazem in the enhancing activity, in spite of their different pharmacological activity. The concentration of free Ca2+ in the HL-60 cells following D3 and/or diltiazem treatment significantly increased. A protein kinase C inhibitor, H-7, inhibited the phenotypic differentiation induced by D3. These results suggest that Ca2+ and protein kinase C play an important role in the differentiation of HL-60 cells induced by D3 and diltiazem.
Taoka
T
T
First Department of Internal Medicine, Kagawa Medical School, Japan.
Itano
T
T
Tokuda
M
M
Tanaka
T
T
Hatase
O
O
Irino
S
S
D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004110:Diltiazem / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology*; D009000:Monocytes / Q000166:cytology*; D010641:Phenotype; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002147:Calmodulin; D011493:Protein Kinase C; D004110:Diltiazem; D002117:Calcitriol; D002118:Calcium