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 Citations (Scopus)

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
StatePublished - May 2005

Fingerprint

Lovastatin
Biosynthetic Pathways
Terpenes
Acute Myeloid Leukemia
Leukemia
Oxidoreductases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Coenzyme A
Blood Cells
Cholesterol
Cell Proliferation

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Lovastatin alters the isoprenoid biosynthetic pathway in acute myelogenous leukemia cells in vivo. / Lewis, Kriste A.; Holstein, Sarah A.; Hohl, Raymond J.

In: Leukemia Research, Vol. 29, No. 5, 05.2005, p. 527-533.

Research output: Contribution to journalArticle

@article{cb397f1897c349e09422965c79605c81,
title = "Lovastatin alters the isoprenoid biosynthetic pathway in acute myelogenous leukemia cells in vivo",
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.",
keywords = "HMG-CoA reductase, Isoprenylation, Lovastatin, Mevalonate pathway, Ras",
author = "Lewis, {Kriste A.} and Holstein, {Sarah A.} and Hohl, {Raymond J.}",
year = "2005",
month = "5",
doi = "10.1016/j.leukres.2004.10.007",
language = "English (US)",
volume = "29",
pages = "527--533",
journal = "Leukemia Research",
issn = "0145-2126",
publisher = "Elsevier Limited",
number = "5",

}

TY - JOUR

T1 - Lovastatin alters the isoprenoid biosynthetic pathway in acute myelogenous leukemia cells in vivo

AU - Lewis, Kriste A.

AU - Holstein, Sarah A.

AU - Hohl, Raymond J.

PY - 2005/5

Y1 - 2005/5

N2 - 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.

AB - 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.

KW - HMG-CoA reductase

KW - Isoprenylation

KW - Lovastatin

KW - Mevalonate pathway

KW - Ras

UR - http://www.scopus.com/inward/record.url?scp=14744273421&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14744273421&partnerID=8YFLogxK

U2 - 10.1016/j.leukres.2004.10.007

DO - 10.1016/j.leukres.2004.10.007

M3 - Article

C2 - 15755505

AN - SCOPUS:14744273421

VL - 29

SP - 527

EP - 533

JO - Leukemia Research

JF - Leukemia Research

SN - 0145-2126

IS - 5

ER -