Impact of alkylphospholipids on the gene expression profile of HaCaT cells.

作者: Geo Semini , Andreas Klein , Kerstin Danker

DOI: 10.1097/FPC.0B013E32834549B9

关键词:

摘要: Objective New alkylphospholipids (APLs) that are structurally derived from the platelet-activating factor (PAF) promising candidates for anticancer treatment. After incorporation into cell membranes, APLs able to interfere with a wide variety of key enzymes implicated in growth, motility, invasion, and apoptosis. In addition prototype 1-O-octadecyl-2-O-methyl-rac-glycero-3- phosphocholine (edelfosine), we presented novel group APLs, glycosidated phospholipids efficiently inhibit proliferation. Two members this group, Ino-C2-PAF Glc-PAF, display high efficacy low cytotoxicity immortalized nontumorigenic skin keratinocyte line, HaCaT. This study investigated impact on transcription whole genome. Materials methods Using Agilent complementary DNA microarray technology, compared global gene expression profiles HaCaT cells treated edelfosine, Ino-C2-PAF, or Glc-PAF profile control cells. Results We found has strongest influence comparison edelfosine Glc-PAF. Gene Ontology analysis showed differentially expressed transcripts regulated by three mainly lipid metabolism, biosynthesis, differentiation, development, ion homeostasis. Nevertheless, most remarkable finding is represented ability downregulate broad spectrum genes associated regulation innate acquired immune response linked inflammation. Conclusion These results identify as effective APL used study. Therefore, might be compound further studies concentrate inhibition inflammatory responses.

参考文章(60)
I A Lampert, Expression of HLA-DR (Ia like) antigen on epidermal keratinocytes in human dermatoses. Clinical and Experimental Immunology. ,vol. 57, pp. 93- 100 ,(1984)
Kerstin Danker, Werner Reutter, Geo Semini, Glycosidated phospholipids: uncoupling of signalling pathways at the plasma membrane British Journal of Pharmacology. ,vol. 160, pp. 36- 47 ,(2010) , 10.1111/J.1476-5381.2009.00626.X
Yvonne Lange, Theodore L Steck, Cholesterol homeostasis. Modulation by amphiphiles. Journal of Biological Chemistry. ,vol. 269, pp. 29371- 29374 ,(1994) , 10.1016/S0021-9258(18)43886-0
María P Carrasco, José M Jiménez‐López, Pablo Ríos‐Marco, Josefa L Segovia, Carmen Marco, None, Disruption of cellular cholesterol transport and homeostasis as a novel mechanism of action of membrane-targeted alkylphospholipid analogues. British Journal of Pharmacology. ,vol. 160, pp. 355- 366 ,(2010) , 10.1111/J.1476-5381.2010.00689.X
Belén Martín-Martín, Manuel Modolell, Faustino Mollinedo, Adalberto Benito, Consuelo Gajate, Jose Luis Fernández-Luna, Rosa Martínez-Dalmau, Selective Induction of Apoptosis in Cancer Cells by the Ether Lipid ET-18-OCH3 (Edelfosine): Molecular Structure Requirements, Cellular Uptake, and Protection by Bcl-2 and Bcl-XL Cancer Research. ,vol. 57, pp. 1320- 1328 ,(1997)
Amy R. Nelson, Barbara Fingleton, Mace L. Rothenberg, Lynn M. Matrisian, Matrix Metalloproteinases: Biologic Activity and Clinical Implications Journal of Clinical Oncology. ,vol. 18, pp. 1135- 1135 ,(2000) , 10.1200/JCO.2000.18.5.1135
Michael H. Runge, Reinhard Andreesen, Albrecht Pfleiderer, Paul G. Munder, Destruction of Human Solid Tumors by Alkyl Lysophospholipids2 JNCI: Journal of the National Cancer Institute. ,vol. 64, pp. 1301- 1306 ,(1980) , 10.1093/JNCI/64.6.1301
Gilbert Arthur, Robert Bittman, THE INHIBITION OF CELL SIGNALING PATHWAYS BY ANTITUMOR ETHER LIPIDS Biochimica et Biophysica Acta. ,vol. 1390, pp. 85- 102 ,(1998) , 10.1016/S0005-2760(97)00163-X