Antiproliferative and cytotoxic profiles of antipsoriatic fumaric acid derivatives in keratinocyte cultures
| Autor: | Bela Sebök, Jürgen Geisel, Bernd Bonnekoh, Gustav Mahrle |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Keratinocytes
Fumaric acid Dimethyl Fumarate chemistry.chemical_element Zinc Calcium Toxicology chemistry.chemical_compound Fumarates Lactate dehydrogenase Humans Psoriasis Cytotoxicity Cells Cultured Pharmacology Cell Death L-Lactate Dehydrogenase Magnesium Biological activity DNA Pollution HaCaT chemistry Biochemistry Protein Biosynthesis Cell Division |
| Zdroj: | European Journal of Pharmacology: Environmental Toxicology and Pharmacology. 270:79-87 |
| ISSN: | 0926-6917 |
| DOI: | 10.1016/0926-6917(94)90083-3 |
| Popis: | Oral administration with complex mixtures of fumaric acid derivatives is known to have antipsoriatic efficacy. The present studies aimed to clarify the mode of action and toxicity of the individual compounds. Hyperproliferative HaCaT keratinocytes in monolayer cultures were exposed to fumaric acid, dimethylfumarate, zinc monoethylfumarate, calcium monoethylfumarate and magnesium monoethylfumarate at concentrations between 0.4 microM and 960 microM for 48 h. Cell proliferation was studied by [3H]thymidine incorporation. In addition 14C-labelled amino acid uptake and total protein content were measured. Direct cytotoxicity was determined by the release of cytoplasmic lactate dehydrogenase (LDH) into the culture medium. The corresponding 50% inhibition concentrations (IC50) were calculated for DNA/protein synthesis: 2.3/2.5 microM (dimethylfumarate), 133/145 microM (zinc monoethylfumarate), 215/230 microM (calcium monoethylfumarate), 275/270 microM (magnesium monoethylfumarate),960/960 microM (fumaric acid). The total protein content was less sensitive. Antiproliferative activity was found for dimethylfumarate and to a lesser degree for calcium monoethylfumarate already at the subtoxic concentrations of 1.3 and 4 microM, respectively. In the case of magnesium monoethylfumarate, zinc monoethylfumarate and fumaric acid there was no such dissociation between their cytotoxic and antiproliferative potential. These data indicate that most of the antipsoriatic potential of fumaric therapies is due to the dimethylfumarate compound. |
| Databáze: | OpenAIRE |
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