Diethylstilbestrol Modifies the Structure of Model Membranes and Is Localized Close to the First Carbons of the Fatty Acyl Chains

The synthetic estrogen diethylstilbestrol (DES) is used to treat metastatic carcinomas and prostate cancer. We studied its interaction with membranes and its localization to understand its mechanism of action and side-effects. We used differential scanning calorimetry (DSC) showing that DES fluidized the membrane and has poor solubility in DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) in the fluid state. Using small-angle X-ray diffraction (SAXD), it was observed that DES increased the thickness of the water layer between phospholipid membranes, indicating effects on the membrane surface. DSC, X-ray diffraction, and P-31-NMR spectroscopy were used to study the effect of DES on the L-proportional to-to-H-II phase transition, and it was observed that negative curvature of the membrane is promoted by DES, and this effect may be significant to understand its action on membrane enzymes. Using the H-1-NOESY-NMR-MAS technique, cross-relaxation rates for different protons of DES with POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) protons were calculated, suggesting that the most likely location of DES in the membrane is with the main axis parallel to the surface and close to the first carbons of the fatty acyl chains of POPC. Molecular dynamics simulations were in close agreements with the experimental results regarding the location of DES in phospholipids bilayers.

Automated summary

This study investigated the interaction and localization of the synthetic estrogen DES with membranes, revealing its effects on membrane surface and enzymes. Experimental techniques including DSC, X-ray diffraction, and NMR spectroscopy provided insights into the mechanisms of action of DES in membranes.