**4.1 Effects derived from lipophilicity of statins**

Lipophilicity of statins is an important factor in the effectiveness of these drugs. Lipophilic statins diffuse passively through the plasma membranes, but hydrophilic statins need transporters to cross them. Hydrophilic statins act mostly in the liver, and lipophilic statins are mainly in extra-hepatic cells [15, 79]. Lipophilicity affects antitumor actions of statins [41] inducing a cell cycle arrest in osteosarcoma [40]. Viability and apoptosis are dependent on lipophilicity, in osteosarcoma [24], chondrosarcoma [41], or rhabdomyosarcoma [43], but no clinical data related to the differential effect of lipophilic *vs* hydrophilic statin in sarcomas were found. Data from other types of tumors show this action [80], being lipophilic statins more effective.
