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: H Grunicke, J Hofmann, K Maly, F Uberall, L Posch, H Oberhuber, H Fiebig
• Journal: Advances in enzyme regulation (Adv Enzyme Regul) Vol. 28 Pg. 201-16 ( 1989) ISSN: 0065-2571 [Print] England
• PMID: 2696343 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Ribosomal Protein S6
• Ribosomal Proteins
• Dexamethasone
• Protein Kinase C
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Division (drug effects)
• Cell Transformation, Neoplastic
• Cells, Cultured
• Dexamethasone (pharmacology)
• Genes, ras
• Kinetics
• Mice
• Phosphorylation
• Protein Kinase C (antagonists & inhibitors)
• Ribosomal Protein S6
• Ribosomal Proteins (metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)
• Transfection