title: Impact of alkylphospholipids on the gene expression profile of HaCaT cells.
abstract: OBJECTIVE
  New alkylphospholipids (APLs) that are structurally derived from the platelet-activating factor (PAF) are promising candidates for anticancer treatment. After incorporation into cell membranes, APLs are able to interfere with a wide variety of key enzymes implicated in cell growth, motility, invasion, and apoptosis. In addition to the prototype 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (edelfosine), we presented a novel group of APLs, the glycosidated phospholipids that efficiently inhibit cell proliferation. Two members of this group, Ino-C2-PAF and Glc-PAF, display high efficacy and low cytotoxicity in immortalized nontumorigenic skin keratinocyte cell line, HaCaT. This study investigated the impact of APLs on the transcription of the whole genome.
  
  
  METHODS
  Using Agilent complementary DNA microarray technology, we compared global gene expression profiles of HaCaT cells treated with edelfosine, Ino-C2-PAF, or Glc-PAF with the profile of control cells.
  
  
  RESULTS
  We found that Ino-C2-PAF has the strongest influence on gene expression in comparison with edelfosine and Glc-PAF. Gene Ontology analysis showed that differentially expressed transcripts regulated by the three APLs are mainly implicated in lipid metabolism, lipid biosynthesis, cell differentiation, cell development, and ion homeostasis. Nevertheless, the most remarkable finding is represented by the ability of Ino-C2-PAF to downregulate a broad spectrum of genes associated with the regulation of the innate and acquired immune response and of genes linked to inflammation.
  
  
  CONCLUSIONS
  These results identify Ino-C2-PAF as the most effective APL used in this study. Therefore, Ino-C2-PAF might be a promising compound for further studies that concentrate on the inhibition of inflammatory responses.
authors.affiliation: Charité-Universitaetsmedizin Berlin, Campus Virchow Klinikum, Institut für Biochemie, Oudenarderstrasse, Germany.
authors.forename: Geo
authors.initials: G
authors.lastname: Semini
authors.forename: Andreas
authors.initials: A
authors.lastname: Klein
authors.forename: Kerstin
authors.initials: K
authors.lastname: Danker
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D015603:Keratinocytes / Q000166:cytology; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; C026659:edelfosine