AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
AIM: 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. MATERIALS AND METHODS: 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. RESULTS: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. CONCLUSION: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.
Authors: Peter Bergman; Charlotte Linde; Katrin Pütsep; Anton Pohanka; Staffan Normark; Birgitta Henriques-Normark; Jan Andersson; Linda Björkhem-Bergman Journal: PLoS One Date: 2011-08-30 Impact factor: 3.240
Authors: Heidrun Karlic; Roman Thaler; Christopher Gerner; Thomas Grunt; Katharina Proestling; Florian Haider; Franz Varga Journal: Cancer Genet Date: 2015-03-18
Authors: Matheus de Castro Fonseca; Andressa França; Rodrigo Machado Florentino; Roberta Cristelli Fonseca; Antônio Carlos Melo Lima Filho; Paula Teixeira Vieira Vidigal; André Gustavo Oliveira; Laurent Dubuquoy; Michael H Nathanson; M Fátima Leite Journal: Am J Physiol Gastrointest Liver Physiol Date: 2018-02-22 Impact factor: 4.871