Abstract
In addition to their lipid-lowering functions, statins elicit additional pleiotropic effects on apoptosis, angiogenesis, inflammation, senescence, and oxidative stress. Many of these effects have been reported in cancerous and noncancerous cells like endothelial cells (ECs), endothelial progenitor cells (EPCs) and human umbilical vein cells (HUVCs). Not surprisingly, statins' effects appear to vary largely depending on the cell context, especially as pertains to modulation of cell cycle, senescence, and apoptotic processes. Perhaps the most critical reason for this discordance is the bias in selecting the applied doses in various cells. While lower (nanomolar) concentrations of statins impose anti-senescence, and antiapoptotic effects, higher concentrations (micromolar) appear to precipitate opposite effects. Indeed, most studies performed in cancer cells utilized high concentrations, where statin-induced cytotoxic and cytostatic effects were noted. Some studies report that even at low concentrations, statins induce senescence or cytostatic impacts but not cytotoxic effects. However, the literature appears to be relatively consistent that in cancer cells, statins, in both low or higher concentrations, induce apoptosis or cell cycle arrest, anti-proliferative effects, and cause senescence. However, statins' effects on ECs depend on the concentrations; at micromolar concentrations statins cause cell senescence and apoptosis, while at nonomolar concentrations statins act reversely.