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      Lovastatin prevents carcinogenesis in a rat model for liver cancer. Effects of ubiquinone supplementation.

      Anticancer research
      Animals, Anticarcinogenic Agents, pharmacology, Apoptosis, drug effects, Body Weight, Cell Growth Processes, Cholesterol, metabolism, Disease Models, Animal, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Liver, anatomy & histology, pathology, Liver Neoplasms, Experimental, prevention & control, Lovastatin, Male, Mevalonic Acid, Organ Size, Precancerous Conditions, drug therapy, Rats, Rats, Inbred F344, Ubiquinone, analogs & derivatives, antagonists & inhibitors, biosynthesis

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          Abstract

          This study tests the hypothesis that statins (HMGCoA reductase inhibitors) inhibit carcinogenesis and that this effect may be mediated by the statin-induced inhibition of ubiquinone synthesis. The effects of lovastatin, with and without addition of ubiquinone, were studied in a rat model for chemically induced hepatocarcinogenesis. Intermediates in the mevalonate pathway were measured. Lovastatin treatment reduced the volume fraction of liver nodules by 50% and the cell proliferation within the liver nodules was reduced to one third. Ubiquinone (Q10) treatment reversed the statin-induced inhibition of cell proliferation. Lathosterol levels were reduced significantly in the statin-treated rats, indicating inhibition of the mevalonate pathway, but cholesterol levels were not affected. Lovastatin inhibits carcinogenesis in a rat model for liver cancer, despite unaffected cholesterol levels. The statin-induced inhibition of cell proliferation may, at least in part, be explained by the inhibition of ubiquinone synthesis.

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