Lovastatin alters the isoprenoid biosynthetic pathway in acute myelogenous leukemia cells in vivo

Kriste A. Lewis, Sarah A. Holstein, Raymond J. Hohl

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)527-533
Number of pages7
JournalLeukemia Research
Volume29
Issue number5
DOIs
Publication statusPublished - May 2005

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Keywords

  • HMG-CoA reductase
  • Isoprenylation
  • Lovastatin
  • Mevalonate pathway
  • Ras

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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