Increase in protein kinase C activity is associated with human fibroblast growth inhibition.
Protein kinase C (PKC) activity and DNA synthesis were measured in human fetal bone marrow fibroblasts following treatment with tumor necrosis factor alpha (TNF alpha) (500 U/ml) or conditioned media containing natural cell proliferation inhibitor (CM-NCPI). Treatment with TNF alpha led to growth stimulation (120 +/- 7% of control in 24 h, 141 +/- 6% in 72 h). At the same time particulate PKC activity diminished, reaching 55 +/- 8% of control in 24 h and remaining at this level at 72 h. CM-NCPI treatment of the cells resulted in a decrease in DNA synthesis (by 39 +/- 6% in 2 h, by 58 +/- 5% in 24 h, and by 78 +/- 8% in 72 h). This was accompanied by a significant rise in particulate PKC activity which increased over 3-fold in 2 h, over 5-fold in 24 h, and up to 11-fold in 72 h. This 11-fold elevation was maintained after 2 week exposure of the fibroblasts to CM-NCPI. The PKC inhibitor neomycin abolished CM-NCPI induced growth inhibition, whereas PKC activator 12-O-tetradecanoylphorbol 13-acetate intensified it. These results suggest that CM-NCPI acts as PKC activator and that negative growth regulation by extracellular agents may involve stimulation of PKC activity.
Rogalsky
V
V
Department of Neoplastic Diseases, Mount Sinai Medical Center, New York, NY 10029.
Todorov
G
G
Den
T
T
Ohnuma
T
T
D001853:Bone Marrow / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D005333:Fetus; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C