title: The phospholipid- and calcium-dependent protein kinase as a target in tumor chemotherapy.
abstract: Evidence for a constitutive activation of protein kinase C (EC 2.7.1.37) in Ha-ras transformed 3T3 cells is presented. Several compounds which inhibit protein kinase C in vitro have been studied with regard to their antiproliferative activity in cultured tumor cells. The following agents were investigated: 3-hexadecyl-mercapto-2-methoxy-methyl-propyl-1- phosphocholine (BM 41440); 1-octadecyl-2-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3); quercetin, tamoxifen and staurosporine. All compounds decrease protein kinase C activity in vitro as well as in intact cells and inhibit cell multiplication within the same dose range. The results suggest a causal relation between the antiproliferative effects and the inhibition of protein kinase C. All inhibitors of protein kinase C synergistically enhance the antiproliferative activity of cis-diamminedichloroplatinum(II). Available data suggest that the effects of protein kinase C inhibitors should be exploitable for tumor chemotherapy.
authors.affiliation: Institut für Medizinische Chemie und Biochemie, Universität Innsbruck, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Grunicke
authors.forename: J
authors.initials: J
authors.lastname: Hofmann
authors.forename: K
authors.initials: K
authors.lastname: Maly
authors.forename: F
authors.initials: F
authors.lastname: Uberall
authors.forename: L
authors.initials: L
authors.lastname: Posch
authors.forename: H
authors.initials: H
authors.lastname: Oberhuber
authors.forename: H
authors.initials: H
authors.lastname: Fiebig
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D011905:Genes, ras; D007700:Kinetics; D051379:Mice; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; D003907:Dexamethasone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate