| Statins are widely used drugs for their role in decreasing cholesterol in hypercholesterolemic patients.
Statins through inhibition of Hydroxy Methyl Glutaryl-CoA Reductase (HMGCR), the main enzyme of the
cholesterol biosynthesis pathway, inhibit mevalonate pathway that provides isoprenoids for prenylation
of different proteins such as Ras superfamily which has an essential role in cancer developing. Inhibition
of the mevalonate/isoprenoid pathway is the cause of the cholesterol independent effects of statins or
pleotropic effects. Depending on their penetrance into the extra-hepatic cells, statins have different effects
on mevalonate/isoprenoid pathway. Lipophilic statins diffuse into all cells and hydrophilic ones use
a variety of membrane transporters to gain access to cells other than hepatocytes.
It has been suggested that the lower accessibility of statins for extra-hepatic tissues may result in the
compensatory induction of mevalonate/isoprenoid pathway and so cancer developing. However, most of
the population-based studies have demonstrated that statins have no effect on cancer developing, even
decrease the risk of different types of cancer.
In this review we focus on the cancer developing “potentials” and the anti-cancer “activities” of statins
regarding the effects of statins on mevalonate/isoprenoid pathway in the liver and extra-hepatic tissues. |