Pleiotropic effects of antitumour alkylphospholipids on cholesterol transport and metabolism.

摘要: Abstract Background Alkylphospholipid (APL) analogs are a new class of membrane-directed synthetic compounds with variety biological actions and clinical applications. In particular, these agents promising candidates in cancer treatment. We have demonstrated that after prolonged treatment APLs alter intracellular cholesterol traffic metabolism human tumor-cell lines, leading to an accumulation inside the cell. After further investigation concerning mode action APLs, we explored influence several on novel aspects lipoprotein homeostasis using hepatoma HepG2 cells THP1-derived macrophages. Methods Quantitative real-time PCR analysis pathway-focused array system was performed measure relative changes mRNA expression number genes related transport metabolism. compared gene-expression profiles treated miltefosine, edelfosine or perifosine for 6 h 24 h profile control cells. also analysed particular interest both macrophage-like THP1 specific assays. Immunoblots were used confirm protein-expression changes. Measurement ABCA1-mediated efflux determined apoA1 as acceptor. Results found global patterns maintain exposure APLs. The pathways biosynthesis LDL-cholesterol uptake transcriptionally upregulated by three assayed. Conversely, major involved catabolism bile acids lipoprotein-associated export impaired APL incubation, which may well contribute higher cell-cholesterol levels induced compounds. Conclusion Incubation different stimulated at same time it depressed common excess removal tumor cells, ultimately altered homeostasis.