The paradoxical effects of statins on the cancer cells and endothelial
cells; the impact of concentrations
Amirhossein Sahebkar
Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran, Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract
Beside their lipid lowering functions, statins impose some additional
effects known as the pleotropic effects. In endothelial progenitor cells
(EPO) and cancer cells statins have been shown to impose the opposite
effects on the cell cycle, senescence and apoptosis. The most
significant reason may arise from bias in selecting the applied doses in
cancer cells compared to those used in EPO cells; in EPOs it was evident
that lower (nanomolar) concentrations of statins impose anti-senescence,
anti-apoptotic, and angiogenic effects; however, higher doses
(micromolar) imposed the adverse effects. In cancer cells, most studies
used high (micromolar) doses of statins showing statins-induced
apoptosis. Some studies indicated that even at low concentrations
(nanomolar) statins induced senescence or imposed cytostatic but not
cytotoxic effects. Regardless of the concentrations, statins in cancer
cells induce apoptosis or cell cycle arrest, anti-proliferation effects,
and cause senescence. However, their effects on EPOs depend on the
concentrations.