Antiproliferative efficacy of lipophilic soy isoflavone phytoestrogens delivered by low density lipoprotein particles into cultured U937 cells

Some fat-soluble bioactive substances incorporated into low density lipopro tein (LDL) may be delivered into cells via LDL receptor pathway influencing cellular functions. In this study, we synthesized a number of fat-soluble isoflavone esters and investigated their incorporation into LDL as well as their delivery into U937 cells. Using an artificial transfer system (Celite dispersion), genistein and daidzein oleates and daidzein dilinoleate were efficiently incorporated into LDL with concentrations ranging between 2.7 t o 16.9 isoflavone molecules/LDL particle, while much smaller amounts of une sterified isoflavones and genistein stearates were transferred into LDL. LD L containing 7-oleates or 4',7-dioleates of genistein and daidzein signific antly reduced U937 cell proliferation by 36-43%. The strongest inhibitory e ffect was shown by daidzein 4',7-dilinoleate with 93% reduction of cell pro liferation Neither of the 4'-oleates of genistein and daidzein contained in LDLs exhibited antiproliferative effects although they were incorporated i nto LDL. In summary, we demonstrated that isoflavones made fat-soluble by e sterification can be incorporated into LDL in vitro and delivered into cult ured U937 cells via the LDL-receptor pathway, reducing the cell proliferati on.