Protein kinase C and adenylate cyclase as targets for growth inhibition of human gastric cancer cells.
In the human gastric adenocarcinoma cell line AGS the effects of the protein-kinase-C-activating phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), the protein kinase C inhibitor staurosporine, the adenylate-cyclase activating agent forskolin, and the permeable dibutyryl-adenosine 3',5'-monophosphate (Bt2cAMP) on the proliferation were assessed. Cell counting followed 5 days of incubation. Prolonged activation of protein kinase C by TPA, inhibition of protein kinase C by staurosporine, activation of adenylate cyclase by forskolin or a direct increase of the intracellular cAMP level all result in a dose-dependent growth inhibition of AGS gastric tumour cells. Half-maximal inhibition was achieved at 100 pM for TPA, 1 nM for staurosporine, 20 microM for forskolin, and 600 microM for Bt2cAMP. It is concluded that protein kinase C and adenylate cyclase play a fundamental role in the growth of AGS gastric cancer cells. Interference with these enzymes involved in the signal transduction of growth regulation in tumour cells may represent a target in the development of new antiproliferative principles.
Piontek
M
M
Department of Gastroenterology, University, Düsseldorf, Germany.
Hengels
K J
KJ
Porschen
R
R
Strohmeyer
G
G
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D019311:Staurosporine; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000067956:Adenylyl Cyclase Inhibitors; D000470:Alkaloids; D005576:Colforsin; D003994:Bucladesine; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate