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Statins and cancer development.

Robin E Duncan1, Ahmed El-Sohemy, Michael C Archer

  • 1Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2.

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
|August 17, 2005
PubMed
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The cholesterol-lowering drug pravastatin may promote extrahepatic cancer by increasing mevalonate synthesis. This occurs because extrahepatic cells do not uptake pravastatin, hindering cholesterol reduction and potentially fueling cancer growth.

Area of Science:

  • Biochemistry
  • Oncology
  • Pharmacology

Background:

  • Epidemiologic studies suggest pravastatin, a hydrophilic HMG-CoA reductase inhibitor, may increase extrahepatic cancer incidence.
  • This association has been largely attributed to chance, but an alternative mechanism is proposed.

Purpose of the Study:

  • To investigate the hypothesis that pravastatin promotes cancer development by inducing HMG-CoA reductase and mevalonate synthesis in extrahepatic tissues.
  • To determine if mevalonate promotes the growth of breast cancer cells.

Main Methods:

  • Investigated the effect of mevalonate on breast cancer cell growth.
  • Examined the mechanism of HMG-CoA reductase induction and mevalonate synthesis in extrahepatic tissues in the context of pravastatin use.

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Main Results:

  • Mevalonate was shown to promote the growth of breast cancer cells.
  • Pravastatin's inhibition of hepatic HMG-CoA reductase leads to decreased circulating cholesterol.
  • Extrahepatic cells lack pravastatin uptake, preventing mitigation of increased mevalonate synthesis.

Conclusions:

  • Pravastatin may promote extrahepatic cancer by inducing HMG-CoA reductase and subsequent mevalonate synthesis.
  • The lack of pravastatin uptake in extrahepatic tissues is a key factor in this proposed mechanism.
  • Mevalonate's role in promoting cancer cell growth warrants further investigation in relation to statin therapy.