The Ether Lipid Inositol-C2-PAF is a Potent Inhibitor of Cell Proliferation in HaCaT Cells
| Autor: | Werner Reutter, Frédéric Cantagrel, Michael Mickeleit, Stephan Laabs, Burkhard Kleuser, Werner Löwe, Annette Fischer, Martin Zimmermann-Kordmann, Dieter Dr. Müller, Kerstin Danker |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Magnetic Resonance Spectroscopy
Biology Biochemistry Mass Spectrometry Cell Line chemistry.chemical_compound Phosphatidylcholine Humans Inositol Platelet Activating Factor Protein Precursors Cytotoxicity Molecular Biology Involucrin Cell Proliferation Transglutaminases Cell growth Organic Chemistry Cell Differentiation Biological activity carbohydrates (lipids) HaCaT Ether lipid chemistry Molecular Medicine lipids (amino acids peptides and proteins) Chromatography Thin Layer |
| Zdroj: | ChemBioChem. 7:441-449 |
| ISSN: | 1439-4227 |
| DOI: | 10.1002/cbic.200500336 |
| Popis: | The search for specific anticancer drugs that do not interfere with DNA synthesis or influence the cytoskeleton has led to the development of modified phospholipids with antiproliferative properties. These compounds cause remodeling of the structure and function of plasma membranes. Recently, we described novel compounds, the glycosidated phospholipids, that surprisingly inhibit cell proliferation. These compounds contain alpha-D-glucose in the sn-2 position of the glycerol backbone of phosphatidylcholine (PC) and platelet-activating factor (PAF), which gives rise to 2-glucophosphatidylcholine (Glc-PC) and 1-O-octadecyl-2-O-alpha-d-glucopyranosyl-sn-2-glycero-3-phosphatidylcholine (Glc-PAF), respectively. Glc-PC and Glc-PAF inhibit the growth of HaCaT cells at nontoxic concentrations. Here we report the introduction of myo-inositol, in place of alpha-D-glucose, in the sn-2 position of the glycerol backbone; this leads to two diastereomeric 1-O-octadecyl-2-O-(2-(myo-inositolyl)-ethyl)-sn-glycero-3-(R/S)-phosphatidylcholines (Ino-C2-PAF). The inositol-containing PAF enhances the antiproliferative capacity (IC(50)=1.8 microM) and reduces the cytotoxicity relative to Glc-PAF (LC(50)=15 microM). Through biological assays, we showed that, in HaCaT cells, Ino-C2-PAF causes upregulation of the keratinocyte-specific differentiation marker involucrin, increases the activity of the differentiation marker transglutaminase, and induces apoptosis at nontoxic concentrations. Ino-C2-PAF therefore seems to be a promising candidate for development as an antiproliferative drug for the treatment of hyperproliferative diseases of the skin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text