The use of
statins has scaled up to become one of the most prescribed medicines in the world and have been very useful in the manegement of
cardiovascular diseases and related mortality. The disclosure of their chemical structure similar to that of hydroxy methyl
glutaryl-CoA (
HMG-CoA) revealed their ability to compete with and inhibit the rate-limiting
enzyme HMG-CoA reductase that catalyzes the synthesis of
mevalonate, which then serves as the precursor for
isoprenoids and
cholesterol in the
mevalonate pathway. While most of the effects of
statins are associated with the lowering of cellular
cholesterol levels, it is clear that they also blunt the non-
sterol branch of the
mevalonate pathway, decreasing formation of
isoprenoids and altering protein-prenylation, a critical event in the posttranslational modulation of
proteins involved in the regulation of cell cycle progression, proliferation and signaling pathways. Randomized controlled trials for the prevention of
cardiovascular diseases indicated that
statins elicited provocative and unexpected benefits for reducing a number of different types of
cancers, including
colorectal carcinoma,
melanoma, prostate and
hepatocellular carcinoma, although in other
cancer types the preclinical expectations of
statins were dissapointing. In this review, we will describe the evidence and mechanisms underlying the potential beneficial use of
statins and the role of protein prenylation in
cancer prevention. Of relevance, the combination of
statins with other anti
cancer drugs may be a significant asset in
malignancies resistant to current
therapy.