TY - JOUR
T1 - Cholesterol inhibition, cancer, and chemotherapy
AU - Buchwald, Henry
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1992/5/9
Y1 - 1992/5/9
N2 - 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 H MG-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.
AB - 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 H MG-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.
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U2 - 10.1016/0140-6736(92)90744-N
DO - 10.1016/0140-6736(92)90744-N
M3 - Article
C2 - 1349377
AN - SCOPUS:0026607503
SN - 0140-6736
VL - 339
SP - 1154
EP - 1156
JO - The Lancet
JF - The Lancet
IS - 8802
ER -