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SHR Neuro Krebs Kardio Lipid

Ramprecht, C; Jaritz, H; Streith, I; Zenzmaier, E; Köfeler, H; Hofmann-Wellenhof, R; Schaider, H; Hermetter, A.
Toxicity of oxidized phosphatidylcholines in cultured human melanoma cells.
Chem Phys Lipids. 2015; 189(136):39-47
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Autor/innen der Med Uni Graz:
Hofmann-Wellenhof Rainer
Köfeler Harald
Ramprecht Claudia
Schaider Helmut
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Abstract:
The oxidized phospholipids (oxPL) 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) and 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) are generated from 1-palmitoyl-2-arachidonoyl-phosphatidylcholine under conditions of oxidative stress. These oxPL are components of oxidized low density lipoprotein. They are cytotoxic in cells of the arterial wall thus playing an important role in the development and progression of atherosclerosis. The toxic lipid effects include inflammation and under sustained exposure apoptosis. The aim of this study was to find out whether such toxic effects, especially apoptosis, are also elicited by oxPL in melanocytic cells in order to assess their potential for therapeutic intervention. FACS analysis after staining with fluorescent markers was performed to identify the mode of lipid-induced cell death. Activation of sphingomyelinase which generates apoptotic ceramide was measured using an established fluorescence assay. Ceramide profiles were determined by mass spectrometry. We found that 50μM POVPC induce cell death in human melanoma cells isolated from different stages of tumor progression but affect primary human melanocytes to a much lesser extent. In contrast, 50μM PGPC was only apoptotic in two out of four cell lines used in this study. The toxicity of both compounds was associated with efficient lipid uptake into the tumor cells and activation of acid sphingomyelinase. In several but not all melanoma cell lines used in this study, activation of the sphingomyelin degrading enzyme correlated with an increase in the concentration of the apoptotic mediator ceramide. The individual patterns of the newly formed ceramide species were also cell line-specific. PGPC and POVPC may be considered potential drug candidates for topical skin cancer treatment. They are toxic in malignant cells. The respective oxidized phospholipids are naturally formed in the body and resistance to these compounds is not likely to occur. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Apoptosis - drug effects
Boron Compounds - chemistry
Cell Line, Tumor -
Ceramides - analysis
Chromatography, High Pressure Liquid -
Chromatography, Reverse-Phase -
Humans -
Lipoproteins, LDL - chemistry
Lipoproteins, LDL - toxicity
Melanoma - metabolism
Melanoma - pathology
Microscopy, Fluorescence -
Oxidation-Reduction -
Phosphatidylcholines - chemistry
Phospholipid Ethers - chemistry
Phospholipid Ethers - toxicity
Sphingomyelin Phosphodiesterase - metabolism

Find related publications in this database (Keywords)
Skin cancer
PGPC
POVPC
Aldehydophospholipid
Apoptosis
Ceramide
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