Binding of daidzein to liposomes.
Turbidity and differential scanning calorimetry measurements revealed the plant derived antineoplastic isoflavone, daidzein, to bind to large unilamellar liposomes. Comparing different unsaturated phospholipids most pronounced aggregation due to daidzein was observed for phosphatidylinositol (PI) while the inclusion of cholesterol strongly attenuated the aggregation. Interestingly, aggregation was not observed for the structurally very closely related isoflavone, genistein. The extent of aggregation was nonlinearly dependent on the content of PI in egg phosphatidylcholine (eggPC) vesicles. The saturated dimyristoyl phospholipids, phosphatidylserine, phosphatidylcholine, phosphatidic acid, as well as phophatidylglycerol were also extensively aggregated by daidzein at 10 degrees C, i.e., below their main phase transition temperature whereas their aggregation at 35 degrees C in the fluid phase was strongly reduced. Vesicle aggregation could be accompanied by membrane fusion, however, neither contents mixing nor lipid mixing of the LUVs (large unilamellar vesicles) was observed in the presence of daidzein. Strong perturbation of the thermal phase behaviour of both dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylserine (DMPS) multilamellar vesicles by daidzein was revealed by differential scanning calorimetry. More specifically, for DMPC increasing quantities of daidzein progressively decreased both the main transition temperature Tm and its enthalpy whereas for DMPS a decrease in delta H was not observed, thus indicating the modes of interaction of daidzein with these phospholipids to differ. Our results indicate daidzein to reside in the polar headgroup/interfacial region of PI and PS membranes. The interactions of daidzein with phospholipids could represent an additional contributor to the growing list of effects of this isoflavone on cellular functions.
Lehtonen
J Y
JY
Department of Medical Chemistry, University of Helsinki, Finland.
Adlercreutz
H
H
Kinnunen
P K
PK
D000970:Antineoplastic Agents / Q000737:chemistry; D001923:Brain Chemistry; D002152:Calorimetry, Differential Scanning; D002784:Cholesterol / Q000737:chemistry; D019833:Genistein; D007529:Isoflavones / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D009994:Osmolar Concentration; D010713:Phosphatidylcholines / Q000737:chemistry; D010716:Phosphatidylinositols / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D012995:Solubility; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007529:Isoflavones; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; C004742:daidzein; D002784:Cholesterol; D019833:Genistein