Statins and cancer development.
There is epidemiologic evidence that the hydrophilic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitor pravastatin increases the incidence of some extrahepatic cancers, although this finding has been attributed to chance. We hypothesize that pravastatin is able to promote the development of cancer by causing an induction of HMG-CoA reductase and, hence, mevalonate synthesis in extrahepatic tissues. We have shown that mevalonate, the product of HMG-CoA reductase, promotes the growth of breast cancer cells. Because there is no uptake of pravastatin by most extrahepatic cells, this statin will be unable to mitigate the increase in mevalonate synthesis in extrahepatic tissues that accompanies the decrease in circulating cholesterol caused by its inhibition of hepatic HMG-CoA reductase.
Duncan
Robin E
RE
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2.
El-Sohemy
Ahmed
A
Archer
Michael C
MC
D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D008798:Mevalonic Acid / Q000378:metabolism; D017035:Pravastatin / Q000009:adverse effects*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin; D008798:Mevalonic Acid