Beyond the "lock and key" paradigm: targeting lipid rafts to induce the selective apoptosis of cancer cells.

Beyond the "lock and key" paradigm: targeting lipid rafts to induce the selective apoptosis of cancer cells. Curr Med Chem. 2018 Jan 10;: Authors: Alves ACS, Dias RA, Kagami LP, das Neves GM, Torres FC, Eifler-Lima VL, Carvalho I, de Miranda Silva C, Kawano DF Abstract For more than 40 years, the fluid mosaic model of cellular membranes have 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 of 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 induces the apoptotic death of cancer cells by recruiting Fas death receptors and the downstream signaling molecules into clusters of lip...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research