Beyond the "Lock and Key" Paradigm: Targeting Lipid Rafts to Induce the Selective Apoptosis of Cancer Cells

Title:Beyond the "Lock and Key" Paradigm: Targeting Lipid Rafts to Induce the Selective Apoptosis of Cancer Cells

Volume: 25 Issue: 18

Author(s): Anna Carolina Schneider Alves, Reinaldo Antonio Dias, Luciano Porto Kagami, Gustavo Machado das Neves, Fernando Cidade Torres, Vera Lucia Eifler-Lima, Ivone Carvalho, Carolina de Miranda Silva and Daniel Fabio Kawano*

Affiliation:

• Faculty of Pharmaceutical Sciences, University of Campinas - UNICAMP, Rua Candido Portinari 200, 13083-871 Campinas-SP,Brazil

Keywords: Lipid rafts, apoptosis, alkylphospholipids, cancer, edelfosine, cell membrane.

Abstract: For more than 40 years, the fluid mosaic model of cellular membranes has supported our vision of an inert lipid bilayer containing membrane protein receptors that are randomly hit by extracellular molecules to trigger intracellular signaling events. However, the notion that compartmentalized cholesterol- and sphingomyelin-rich membrane microdomains (known as lipid rafts) spatially arrange receptors and effectors to promote kinetically favorable interactions necessary for the signal transduction sounds much more realistic. Despite their assumed importance for the dynamics of ligand-receptor interactions, lipid rafts and biomembranes as a whole remain less explored than the other classes of biomolecules because of the higher variability and complexity of their membrane phases, which rarely provide the detailed atomic-level structural data in X-ray crystallography assays necessary for molecular modeling studies. The fact that some alkylphospholipids (e.g. edelfosine: 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) selectively induce the apoptotic death of cancer cells by recruiting Fas death receptors and the downstream signaling molecules into clusters of lipid rafts suggests these potential drug targets deserve a more in-depth investigation. Herein, we review the structure of lipid rafts, their role in apoptotic signaling pathways and their potential role as drug targets for the treatment of cancer.

Cite this article as:

Alves Carolina Schneider Anna , Dias Antonio Reinaldo, Kagami Porto Luciano , das Neves Machado Gustavo, Torres Cidade Fernando, Eifler-Lima Lucia Vera , Carvalho Ivone, de Miranda Silva Carolina and Kawano Fabio Daniel *, Beyond the "Lock and Key" Paradigm: Targeting Lipid Rafts to Induce the Selective Apoptosis of Cancer Cells, Current Medicinal Chemistry 2018; 25 (18) . https://dx.doi.org/10.2174/0929867325666180111100601