Cholesterol inhibition, cancer, and chemotherapy.
An important feature of malignant transformation is loss of the cholesterol feedback inhibition mechanism that regulates cholesterol synthesis. Cancer cells seem to require an increase in the concentrations of cholesterol and of cholesterol precursors. Therefore, a reasonable assumption is that prevention of tumour-cell growth can be achieved by restricting either cholesterol availability or cholesterol synthesis. In-vivo and cell-culture experiments have shown that lowering the plasma cholesterol concentration or intervening in the mevalonate pathway with 3-hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitors decreases tumour growth. Currently prescribed doses of HMG-CoA reductase inhibitors given orally or continuously by an implantable infusion pump could achieve tumour therapeutic tissue concentrations of these agents. My hypothesis is that cholesterol inhibition can inhibit tumour cell growth, can act as an adjuvant to cancer chemotherapy, and, possibly, can prevent carcinogenesis.
Buchwald
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Department of Surgery, UMHC, University of Minnesota, Minneapolis 55455.
D000277:Adjuvants, Pharmaceutic; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000494:pharmacology / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008148:Lovastatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008798:Mevalonic Acid / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000209:etiology*; D009374:Neoplasms, Experimental / Q000209:etiology*; D051381:Rats
D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; D002784:Cholesterol; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid