10 research outputs found
A short-term statin treatment changes the contractile properties of fast-twitch skeletal muscles
Abrogation of insulin-like growth factor-I (IGF-I) and insulin action by mevalonic acid depletion: synergy between protein prenylation and recep glycosylation pathways.
Atorvastatin affects the serum lipoprotein profile and cardiovascular risk in acromegaly.
Atorvastatin administration is associated with does-related changes in IGF bioavailability
Insulin-like Growth Factor Binding Protein-1 and Interleukin-6 are Markers of Fetal Stress During Parturition at Term Gestation
In vitro and in vivo anticancer effects of mevalonate pathway modulation on human cancer cells.
BackgroundThe increasing usage of statins (the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) has revealed a number of unexpected beneficial effects, including a reduction in cancer risk.MethodsWe investigated the direct anticancer effects of different statins approved for clinical use on human breast and brain cancer cells. We also explored the effects of statins on cancer cells using in silico simulations.ResultsIn vitro studies showed that cerivastatin, pitavastatin, and fluvastatin were the most potent anti-proliferative, autophagy inducing agents in human cancer cells including stem cell-like primary glioblastoma cell lines. Consistently, pitavastatin was more effective than fluvastatin in inhibiting U87 tumour growth in vivo. Intraperitoneal injection was much better than oral administration in delaying glioblastoma growth. Following statin treatment, tumour cells were rescued by adding mevalonate and geranylgeranyl pyrophosphate. Knockdown of geranylgeranyl pyrophosphate synthetase-1 also induced strong cell autophagy and cell death in vitro and reduced U87 tumour growth in vivo. These data demonstrate that statins main effect is via targeting the mevalonate synthesis pathway in tumour cells.ConclusionsOur study demonstrates the potent anticancer effects of statins. These safe and well-tolerated drugs need to be further investigated as cancer chemotherapeutics in comprehensive clinical studies