Izvorni znanstveni članak
Influence of cancerostatic perifosine on membrane fluidity of liposomes and different cell lines as measured by electron paramagnetic resonance
Rok Podlipec
; Center of excellence NAMASTE Ljubljana, Slovenia
Tilen Koklic
; Jožef Stefan Institute, Ljubljana Slovenia
Janez Štrancar
; Jožef Stefan Institute, Ljubljana Slovenia
Janez Mravljak
; Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
Marjeta Šentjurc
; Jožef Stefan Institute, Ljubljana Slovenia
Sažetak
Ključne riječi
Aim To test whether membrane fluidity and its changes are important for the sensitivity of cells to the action of perifosine (OPP); a new anticancer drug targeting cell membrane and not DNA. Method Influence of OPP on the membrane structure of OPP-resistant MCF7; and OPP-sensitive MT3 breast cancer cell lines; as well as of mouse fibroblasts (L929) cell lines; and model cells (liposomes) was investigated by electron paramagnetic resonance; using spin labeled derivative of OPP (P5) and 5-doxylpalmitoyl methylester (MeFASL(10; 3)) as spin probes. Results OPP increased membrane fluidity of all cell lines at concentrations higher than 50 μM (on the level of P ≤ 0.05; t test). In cells; the differences were observed only by P5 and not by MeFASL(10; 3). Average order parameter Seff decreased for about 12% in MCF7 and L929 and only for 8% in OPP-sensitive MT3 cells; showing that there was no correlation between membrane fluidity changes and sensitivity of cells to OPP. The only correlation we found was between OPP sensitivity and the cell growth rate. In liposomes; both spin probes were sensitive to the action of OPP. Seff decreased with increasing concentration of OPP. For MeFASL(10; 3) a significant decrease was observed at 4 mol% OPP; while for P5 it was observed at 8 mol%. Conclusion Influence of OPP on plasma membrane fluidity of breast cancer cells is not the determining factor in the sensitivity of cells to OPP
Hrčak ID:
94996
URI
Datum izdavanja:
15.12.2012.
Posjeta: 1.405 *