Monday 9 May 2005
Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is required for cholesterol biosynthesis, and are beneficial in the primary and secondary prevention of cardiovascular disease. Most of the benefits of statin therapy are owing to the lowering of serum cholesterol levels.
However, by inhibiting HMG-CoA reductase, statins can also inhibit the synthesis of isoprenoids, which are important lipid attachments for intracellular signaling molecules, such as Rho, Rac and Cdc42.
Therefore, it is possible that statins might exert cholesterol-independent or ’pleiotropic’ effects through direct inhibition of these small GTP-binding proteins.
Statins might have important roles in diseases that are not mediated by cholesterol.
Statins and cancer
These findings have led to the intensive study of statins in cancer prevention, including recent, large population-based studies showing statin-associated reductions in overall, colorectal and prostate cancer.
Understanding the complex cellular effects (for example, on angiogenesis and inflammation) and the underlying molecular mechanisms of statins (for example, 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase-dependent processes that involve geranylgeranylation of Rho proteins, and HMG-CoA-independent processes that involve lymphocyte-function-associated antigen 1) will advance the development of molecularly targeted agents for preventing cancer.
Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell ’stemness’ via the bone morphogenetic protein pathway (BMPs) (21551187)
Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell ’stemness’ via the bone morphogenetic protein pathway (BMPs). Kodach LL, Jacobs RJ, Voorneveld PW, Wildenberg ME, Verspaget HW, van Wezel T, Morreau H, Hommes DW, Peppelenbosch MP, van den Brink GR, Hardwick JC. Gut. 2011 Nov;60(11):1544-53. PMID: 21551187
Wang CY, Liu PY, Liao JK. Pleiotropic effects of statin therapy: molecular mechanisms and clinical results. Trends Mol Med. 2007 Dec 6; PMID: 18068482
Menge T, Hartung HP, Stuve O. Statins—a cure-all for the brain? Nat Rev Neurosci. 2005 Apr;6(4):325-31. PMID: 15803163