Induction of differentiation of HL-60 cells by protein kinase C inhibitor, K252a.
To clarify the role of protein kinase C and protein kinase A in cell proliferation and differentiation, the effects of K252a and its derivatives (K252b, KT5720), which have different inhibitory activity to these protein kinases, on the proliferation and differentiation of HL-60 cells were investigated. The proliferation and DNA synthesis of the HL-60 cells were inhibited by K252a in a dose dependent manner. However, K252b and KT5720 which are more specific inhibitors of protein kinase C or protein kinase A, respectively, had no observable effect on cell proliferation. K252a (40nM) enhanced the differentiation of HL-60 cells induced by 1,25(OH)2D3, retinoic acid and DMSO. K252b and KT5720 did not affect 1,25(OH)2D3-induced differentiation. K252a significantly inhibited the differentiation induced by PMA. These results demonstrate that K252a but not its derivatives can function as an antitumor drug and enhancer of the differentiation induced by various inducers.
Taoka
T
T
Division of Biomedical Sciences, University of California, Riverside 92521.
Tokuda
M
M
Tasaka
T
T
Hatase
O
O
Irino
S
S
Norman
A W
AW
D002227:Carbazoles / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D026121:Indole Alkaloids; D007211:Indoles / Q000494:pharmacology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D002227:Carbazoles; D004273:DNA, Neoplasm; D026121:Indole Alkaloids; D007211:Indoles; D011758:Pyrroles; C057416:KT 5720; C049985:staurosporine aglycone; D011494:Protein Kinases; D011493:Protein Kinase C