Document Detail


Glycosidated phospholipids: uncoupling of signalling pathways at the plasma membrane.
MedLine Citation:
PMID:  20331609     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cell expansion and metastasis are considered hallmarks of tumour progression. Therefore, efforts have been made to develop novel anti-cancer drugs that inhibit both the proliferation and the motility of tumour cells. Synthetic alkylphospholipids, compounds with aliphatic side chains that are ether linked to a glycerol backbone, are structurally derived from platelet-activating factor and represent a new class of drugs with anti-proliferative properties in tumour cells. These compounds do not interfere with the DNA or mitotic spindle apparatus of the cell. Instead, they are incorporated into cell membranes, where they accumulate and interfere with lipid metabolism and lipid-dependent signalling pathways. Recently, it has been shown that the most commonly studied alkylphospholipids inhibit proliferation by inducing apoptosis in malignant cells while leaving normal cells unaffected. This review focuses on a novel group of synthetic alkylphospholipids, the glycosidated phospholipids, which contain carbohydrates or carbohydrate-related molecules at the sn-2 position of the glycerol backbone. Members of this subfamily also exhibit anti-proliferative capacity and modulate the cell adhesion, differentiation, and migration of tumour cells. Among this group, Ino-C2-PAF shows the highest efficacy and low cytotoxicity. Apart from its anti-proliferative effect, Ino-C2-PAF strongly reduces cell motility via its inhibitory effect on the phosphorylation of the cytosolic tyrosine kinases FAK and Src. Signalling pathways under the control of the FAK/Src complex are normally required for both migration and proliferation and play a prominent role in tumour progression. We intend to highlight the potential of glycosidated phospholipids, especially Ino-C2-PAF, as a promising new group of drugs for the treatment of hyperproliferative and migration-based skin diseases.
Authors:
Kerstin Danker; Werner Reutter; Geo Semini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2010-03-19
Journal Detail:
Title:  British journal of pharmacology     Volume:  160     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-23     Completed Date:  2010-07-26     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  36-47     Citation Subset:  IM    
Affiliation:
Charité-Universitaetsmedizin Berlin, Campus Mitte, Institut fuer Biochemie, Monbijoustr, Berlin. kerstin.danker@charite.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / adverse effects,  pharmacology*
Cell Membrane / metabolism
Cell Movement / drug effects
Cell Proliferation / drug effects
Glycosides / adverse effects,  pharmacology*
Humans
Inositol / adverse effects,  analogs & derivatives,  pharmacology
Molecular Structure
Neoplasm Metastasis
Neoplasms / drug therapy,  pathology
Phospholipids / adverse effects,  pharmacology*
Platelet Activating Factor / adverse effects,  analogs & derivatives,  pharmacology
Signal Transduction
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Glycosides; 0/Phospholipids; 0/Platelet Activating Factor; 6917-35-7/Inositol
Comments/Corrections

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