Inhibition of DNA synthesis by protein kinase C-activating phorbol esters in NIH/3T3 cells.
Fibroblast growth factor (FGF) plus insulin induced DNA synthesis in and proliferation of NIH/3T3 cells. The protein kinase C-activating phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), inhibited both the DNA synthesis and cell proliferation induced by FGF plus insulin. The concentration of TPA required for 50% inhibition of the DNA synthesis was about 5 nM. Phorbol-12,13-dibutyrate, another protein kinase C-activating phorbol ester, also inhibited the DNA synthesis but 4 alpha-phorbol-12,13-didecanoate, known to be inactive for this enzyme, was ineffective. DNA synthesis started at about 12 h after the addition of FGF plus insulin. The inhibitory action of TPA on the DNA synthesis was observed when it was added within 12 h after the addition of FGF plus insulin. These results suggest that phorbol esters exhibit an antiproliferative action through protein kinase C activation in NIH/3T3 cells, and that this action of phorbol esters is due to inhibition of the progression from the late G1 to the S phase of the cell cycle.
Yamamoto
T
T
Department of Biochemistry, Kobe University School of Medicine, Hyogo.
Tsuda
T
T
Hamamori
Y
Y
Nishimura
N
N
Takai
Y
Y
D000818:Animals; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D004789:Enzyme Activation; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007328:Insulin; D010703:Phorbol Esters; C008876:phorbol-12,13-didecanoate; D015240:Phorbol 12,13-Dibutyrate; D005346:Fibroblast Growth Factors; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate