Journal
LEUKEMIA RESEARCH
Volume 29, Issue 5, Pages 527-533Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2004.10.007
Keywords
lovastatin; mevalonate pathway; Ras; HMG-CoA reductase; isoprenylation
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Lovastatin, a competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase (HMGR), is used therapeutically to lower plasma cholesterol levels and has garnered attention for its cytotoxic effects in leukemia cells. In this study, escalating doses of lovastatin were administered to nine patients with acute myelogenous leukemia. Peripheral blood leukemia cells were drawn pre- and post-lovastatin dosing. Plasma lovastatin bioactivity ranged up to 234 nM lovastatin equivalents. Our results show that in vivo lovastatin, at up to 200 mg/dose, induces an increased activity of leukemia cell HMGR and alters leukemia cell proliferation without discernibly altering Ras processing. (c) 2004 Elsevier Ltd. All rights reserved.
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