Skip to main content
padlock icon - secure page this page is secure

Anticancer Alkylphospholipids: Mechanisms of Action, Cellular Sensitivity and Resistance, and Clinical Prospects

Buy Article:

$63.00 + tax (Refund Policy)

Synthetic anticancer alkylphospholipids (APLs), such as edelfosine, miltefosine and perifosine, are a group of structurally related lipids that act on cellular membranes rather than the DNA. APLs have essentially one long hydrocarbon chain that allows easy partitioning into membrane lipid bilayers, but they resist catabolic degradation. APLs therefore accumulate in cell membranes and can interfere with normal lipid metabolism and lipid-dependent signal transduction. This action, often leading to apoptosis, is most effective in metabolically active, proliferating cells, such as cancer cells, but not in quiescent normal cells. This review describes the general mechanisms of APL cellular uptake and action. Most important for their biological effect are the inhibition of phosphatidylcholine synthesis, the inhibition of the MAPkinase/ ERK proliferative and phosphatidylinositol 3-kinase/ Akt survival pathways and the stimulation of the Stressactivated protein kinase/JNK pathway, which may lead to apoptosis in cancer cells. APLs are most promising in combination with conventional cancer therapies. For example, ALPs increase the cancer cell sensitivity to radiotherapy in vitro and in vivo. We highlight the clinical potential of perifosine, an orally available APL.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Keywords: Anticancer ether lipids; alkylphospholipids; apoptosis; edelfosine; erucylphosphocholine; miltefosine; perifosine; signal transduction

Document Type: Research Article

Affiliations: Netherlands Cancer Institute,Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.

Publication date: 01 July 2008

More about this publication?
  • Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

    Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.
  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more