Ligands of the antiestrogen binding site block endothelial cell proliferation reversibly

Benzylphenoxyethanamine derivatives are known to display antiproliferative activities on tumor cell lines consistently with their binding affinity to the microsomal antiestrogen binding site. In the present study we show that pyrrolidinobenzylphenoxyethanamine, a new efficient compound of this series, exhibits reversible effects on exponentially growing adult bovine aortic endothelial cells inducing (1) lamellated cytoplasmic inclusions, (2) cell proliferation inhibition, (3) dose-dependent transition delay of cells in the G0-G1 phase of the cell cycle. Complete reversal of these effects is achieved only by withdrawing the drug from the medium. The ultrastructural cellular modifications disappeared, and flow cytometry and thymidine incorporation analysis showed the effect on degree of synchronization of this one-step methodology.