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


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.


CONCLUSIONS
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.
Björkhem-Bergman
Linda
L
Division of Clinical Pharmacology C1-68, Karolinska University Hospital, Huddinge, Karolinska Institutet, Stockholm, Sweden. linda.bjorkhem-bergman@karolinska.se
Acimovic
Jure
J
Torndal
Ulla-Britta
UB
Parini
Paolo
P
Eriksson
Lennart C
LC
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014451:Ubiquinone; D002784:Cholesterol; D008148:Lovastatin; C024989:coenzyme Q10; D008798:Mevalonic Acid