A comparative study of the effects of cholesterol and sclareol, a bioactive labdane type diterpene, on phospholipid bilayers.
Sclareol (labd-14-ene-8,13-diol) is a highly water-insoluble molecule that belongs to the labdane type diterpenes and is characterized as a biologically active molecule, due to its cytotoxic and cytostatic effects against human leukemic cell lines. A superimposition study between sclareol and cholesterol, based on their corresponding hydrophobic and polar molecular segments calculated from their lipophilic profiles, revealed their spatial similarities. This structural similarity between the two molecules prompted us to compare their effects on the structure and stability of phospholipid dipalmitoylphosphatidylcholine (DPPC) membranes. Differential scanning calorimetry (DSC) was applied to compare the thermal changes caused by either cholesterol or sclareol when are incorporated in DPPC bilayers. The results showed that sclareol is incorporated into phospholipid model membranes and mimics the thermal effects of cholesterol especially at concentrations up to X(sclareol)=9.1 mol%. These effects can be summarized as the abolition of pre-transition, lowering of the main phase transition and reduction of the enthalpy change (DeltaH) of the gel to liquid-crystalline phase transition of DPPC bilayers. At concentrations X> or =16.7 mol%, sclareol and cholesterol caused different heterogeneity in lipid bilayers or a reversible transition from a vesicular suspension to an extended peak bilayer network. This different fluidization, exerted by the two molecules at high concentration, may be related to their different stability and the z-average mean diameter of the liposomes they form. Small unilamellar vesicles, prepared by the thin film hydration method showed that DPPC bilayers containing a high concentration of sclareol in equimolar ratio sclareol:cholesterol were unstable, in contrast to the ones containing only cholesterol.
Kyrikou
I
I
Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, Vasileos Constantinou 48, Athens 11635, Greece.
Georgopoulos
A
A
Hatziantoniou
S
S
Mavromoustakos
T
T
Demetzos
C
C
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002784:Cholesterol / Q000737:chemistry*; D004224:Diterpenes / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D015394:Molecular Structure; D044367:Phase Transition; D013816:Thermodynamics
D004224:Diterpenes; D008051:Lipid Bilayers; D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol; C070760:sclareol