Title:Statins and Cancer
Volume: 14
Issue: 5
Author(s): Natalia G. Vallianou, Alexandra Kostantinou, Marios Kougias and Christos Kazazis
Affiliation:
Keywords:
Cancer, chemotherapy, statin, mechanisms, mortality.
Abstract: Statins have pleiotropic properties and might exert an effect even in the field of cancer. Statins competitively inhibit
3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase, the major rate-limiting enzyme that controls the conversion of HMG-CoA
to mevalonic acid. Specifically, inhibition of HMG-CoA reductase by statins has been proved to prevent the synthesis of mevalonic acid,
a precursor of non-steroidal isoprenoids, which are lipid attachment molecules for small G proteins, such as Ras, Rho and Rac. Thus,
statins may inhibit the synthesis of isoprenoids and thereby suppress the activation of small G proteins.
In addition, statins exert pro-apoptotic, anti-angiogenic, and immunomodulatory effects, which may prevent cancer growth. Statins may
inhibit the growth of a variety of cancer cell types, including breast, gastric, pancreatic, and prostate carcinoma, neuroblastoma,
melanoma, mesothelioma and acute myeloid leukemia cells. They exert pro-apoptotic effects in a wide range of cancer cell lines, but with
many differences in the sensitivity to statin-induced cell death among different cancer cell types. Regarding anti-angiogenic effects,
multiple statin effects on blood vessel formation by inhibition of angiogenesis through down-regulation of pro-angiogenic factors, such as
vascular endothelial growth factor, inhibition of endothelial cell proliferation and inhibition of adhesion to extracellular matrix by
blocking intercellular adhesion molecules have been suggested. The molecular mechanisms of statin immunomodulation often implicate
multiple pathways, regarding the regulation of genes encoding key molecules, which are involved in antigen presentation and subsequent
immunomodulation. Another mechanism involves the down-regulation of the nuclear factor-kappa-B, which is responsible for the
transcription of many genes involved in immunologic mechanisms, such as interferon-inducible protein-10, monocyte chemo-attractant
protein 1 and cyclooxygenase-2.
Statins have been associated with a significantly lower risk of breast, colorectal, ovarian, pancreatic, lung cancers and lymphoma in
several observational studies. On the other hand, other studies, including meta-analyses have raised concerns about the safety of statins
among elderly patients. A recent study upon the relationship between statin use (prior to cancer diagnosis) and cancer-related mortality in
the entire Danish population from 1995-2009 in adults > 40 years of age has been conducted. As compared to statin non-users, patients
using statins prior to cancer diagnosis were 15% less likely to die from any cause or cancer specifically. Further investigation is needed to
elaborate on their mode of action as well as their true significance on cancer prevention and perhaps as an adjuvant to cancer
chemotherapy.
