Statins and Cancer Development
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Requests for reprints:
Michael C. Archer, Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2. Phone: 416-978-8195; Fax: 416-971-971-2366. E-mail: m.archer{at}utoronto.ca
Abstract
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.
- Statins
- Mevalonate
- HMG-CoA reductase
- Epidemiology
- Prevention
- Tumor promotion and progression
- Agents with other mechanisms of action
Footnotes
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Grant support: U.S. Army Medical Acquisition Activity grant DAMD17-99-1-9409. The content of the information does not necessarily reflect the position or the policy of the US Government and no official endorsement should be inferred.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted May 16, 2005.
- Received January 12, 2005.
- Revision received May 4, 2005.
