Statins have been widely used for the treatment of hypercholesterolemia and other cardiovascular diseases. Recently, statins have been studied for their apoptotic effects, making them relevant for cancer prevention and treatment; however, their exact mechanisms of action are still unclear. In this study, we used malignant UMR-106 osteosarcoma cells and normal HTR8/SVneo extravillous trophoblast cells, and found that simvastatin decreases cell viability in a dose and time-dependent manner in both cell types. In addition, 10 µM simvastatin was able to induce apoptosis in trophoblast cells, as evaluated by FACS analysis. Finally, proteomic analysis of protein expression suggests a specific regulatory mechanism that could explain some of the anticancer effects of this statin.