Changes in biophysical parameters of plasma membranes influence cisplatin resistance of sensitive and resistant epidermal carcinoma cells.
The mechanism of resistance of cancer cells to the anticancer drug cisplatin is not fully understood. Using cisplatin-sensitive KB-3-1 and -resistant KCP-20 cells, we found that the resistant cells have higher membrane potential, as determined by membrane potential sensing oxonol dye. Electron spin resonance and fluorescence polarization studies revealed that the resistant cells have more "fluid" plasma membranes than the sensitive cells. Because of this observed difference in membrane "fluidity," we attempted modification of the plasma membrane fluidity by the incorporation of heptadecanoic acid into KB-3-1 and KCP-20 cell membranes. We found that such treatment resulted in increased heptadecanoic acid content and increased fluidity in the plasma membranes of both cell types, and also resulted in increased cisplatin resistance in the KCP-20 cells. This finding is in accord with our results, which showed that the cisplatin-resistant KCP-20 cells have more fluid membranes than the cisplatin-sensitive KB-3-1 cells. It remains to be determined whether the observed differences in biophysical status and/or fatty acid composition alone, or the secondary effect of these differences on the structure or function of some transmembrane protein(s), is the reason for increased cisplatin resistance.
Liang
Xing-Jie
XJ
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Room 1A-09, 37 Convent Drive, Bethesda, MD 20892-4254, USA.
Yin
Jun-Jie
JJ
Zhou
Jien-Wei
JW
Wang
Paul C
PC
Taylor
Barbara
B
Cardarelli
Carol
C
Kozar
Michael
M
Forte
Raynard
R
Aszalos
Adorjan
A
Gottesman
Michael M
MM
D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D002999:Clone Cells; D003497:Cyclic N-Oxides; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007555:Isoxazoles; D008560:Membrane Fluidity / Q000187:drug effects / Q000235:genetics*; D008563:Membrane Lipids / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015221:Potassium Channels / Q000378:metabolism; D011744:Pyrimidinones
D003497:Cyclic N-Oxides; D005227:Fatty Acids; D007555:Isoxazoles; D008563:Membrane Lipids; D008565:Membrane Proteins; D015221:Potassium Channels; D011744:Pyrimidinones; C018622:oxonol dyes (isoxazole); C005072:5-doxylstearic acid; C003954:merocyanine dye; D002945:Cisplatin; C013102:margaric acid