Biomaterial Database

Differential inhibition by staurosporine, a potent protein kinase C inhibitor, of 12-O-tetradecanoylphorbol-13-acetate-caused skin tumor promotion, epidermal ornithine decarboxylase induction, hyperplasia and inflammation. 1989

S Yamamoto, and I Kiyoto, and E Aizu, and T Nakadate, and Y Hosoda, and R Kato

Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.

The effect of staurosporine on 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin papilloma formation was examined in CD-1 mice. A topical application of staurosporine 15 min prior to each TPA treatment resulted in a dose-related inhibition of tumor formation. Staurosporine by itself had no tumor producing activity in DMBA-initiated mice. Staurosporine failed to prevent TPA-induced edema formation, whereas quercetin markedly suppressed it. Staurosporine by itself did not induce a significant edema. Histological studies revealed that staurosporine failed to inhibit TPA-induced inflammation but rather augmented TPA-induced polymorphonuclear leukocyte (PMN) infiltration. Staurosporine by itself induced a slight PMN infiltration 1 h after the drug application, but the effect was only transient. Although staurosporine failed to inhibit the TPA-induced epidermal hyperplasia and DNA synthesis significantly, nuclear atypism of the superficial layer of the epidermis appeared to be less remarkable in staurosporine-pretreated mice. TPA-caused epidermal ornithine decarboxylase (ODC) induction was not inhibited by staurosporine but rather augmented by this agent. TPA enhanced the phosphorylation of 34 kd protein in intact epidermal cells in a concentration-dependent manner. Staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) suppressed the TPA-stimulated phosphorylation of 34 kd protein, but palmitoylcarnitine failed to suppress it. In addition, TPA-stimulated superoxide generation of rabbit peritoneal PMN was potently inhibited by staurosporine. It is possible that TPA induces inflammation, ODC activity, epidermal hyperplasia and tumor promotion through the activation of different type(s) of protein kinase C and staurosporine inhibits only certain type(s) of protein kinase C. Another possible explanation is that the protein kinase C inhibition by staurosporine depends on the nature of the substrate proteins or the intracellular localization of the enzyme.

UI	MeSH Term	Description	Entries
D006965	Hyperplasia	An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells.	Hyperplasias
D007249	Inflammation	A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008815	Mice, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.	Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009955	Ornithine Decarboxylase	A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated S-adenosylmethionine to form spermidine.	Ornithine Carboxy-lyase,Carboxy-lyase, Ornithine,Decarboxylase, Ornithine,Ornithine Carboxy lyase
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D012016	Reference Values	The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.	Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D004487	Edema	Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.	Dropsy,Hydrops,Anasarca
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D005260	Female		Females