Effects of activators and inhibitors of protein kinase C on two-stage transformation in BALB/3T3 cells.
To determine the relationship between protein kinase C and the promotion of carcinogenesis, we investigated the effects of activators and inhibitors of protein kinase C on two-stage transformation in BALB/3T3 cells. Diacylglycerols, which are activators, and specific inhibitors, such as palmitoyl-DL-carnitine chloride (PC), 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), and staurosporine (ST) were used. Treatment with diacylglycerols enhanced focus formation in 3-methylcholanthrene (3-MC)-initiated cells, but not as much as 12-O-tetradecanoylphorbol-13-acetate (TPA). PC and H-7 inhibited TPA-enhanced transformation by 76 and 79%, respectively. ST, the most potent inhibitor of protein kinase C, had a low inhibitory effect on transformation at non-toxic doses (33% inhibition). The results suggest that protein kinase C may play an important role in the process by which transformation is promoted in BALB/3T3 cells.
Semba
M
M
Laboratory of Cell Toxicology, Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan.
Inui
N
N
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002460:Cell Line / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism; D003043:Cocarcinogenesis; D004075:Diglycerides / Q000494:pharmacology*; D004336:Drug Antagonism; D004789:Enzyme Activation / Q000187:drug effects; D005989:Glycerides / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008748:Methylcholanthrene / Q000633:toxicity*; D051379:Mice; D010172:Palmitoylcarnitine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D000470:Alkaloids; D004075:Diglycerides; D005989:Glycerides; D007546:Isoquinolines; D010879:Piperazines; D010172:Palmitoylcarnitine; D008748:Methylcholanthrene; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate