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Inhibition of the G1/S transition in A65 cells by H-7, a protein kinase C inhibitor.

Authors
Type
Published Article
Journal
Biochemical Pharmacology
0006-2952
Publisher
Elsevier
Publication Date
Volume
45
Issue
3
Pages
772–775
Identifiers
PMID: 8442775
Source
Medline
License
Unknown

Abstract

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.

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