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.