Inhibition of the G1/S transition in A65 cells by H-7, a protein kinase C inhibitor.
The effects of protein kinase inhibitors on the proliferation of A65 murine leukemia cells were studied. The proliferation of phorbol ester-dependent A65 cells was inhibited by N-(2-methylpiperazyl)-5-isoquinolinesulfonamide (H-7), a protein kinase C inhibitor, at a significantly lower concentration than the phorbol ester-independent variant, while both cell types had the same sensitivity to N-[2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl]amino]ethyl]-5- isoquinolinesulfonamide, a selective inhibitor of protein kinase A, and staurosporine, a non-selective inhibitor of protein kinases. When the effect of H-7 on the cell cycle was analysed by flow-cytometry, the agent at concentrations that completely inhibited the cell proliferation significantly increased the proportion in the G0/G1 phase of both cell types but decreased that in the S phase, without much change in the G2/M phase. These results suggest that H-7 blocks the G1/S transition by inhibiting protein kinase C, whether the proliferation is dependent on phorbol ester or not.
Miyamoto
K
K
Research Laboratory for Development of Medicine, School of Pharmacy, Hokuriku University, Kanazawa, Japan.
Nakamura
S
S
Ikeda
K
K
Nomura
M
M
Wakusawa
S
S
Hidaka
H
H
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology*; D007942:Leukemia, Experimental; D051379:Mice; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D016196:S Phase / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D007546:Isoquinolines; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C