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

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

doi:10.1016/j.leukres.2004.10.007

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 journal › Article › peer-review

34 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 language	English (US)
Pages (from-to)	527-533
Number of pages	7
Journal	Leukemia Research
Volume	29
Issue number	5
DOIs	https://doi.org/10.1016/j.leukres.2004.10.007
State	Published - May 2005

All Science Journal Classification (ASJC) codes

Hematology
Oncology
Cancer Research

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.leukres.2004.10.007

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@article{b125637894ea47c3894e1a2622787c04,

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.",

author = "Lewis, {Kriste A.} and Holstein, {Sarah A.} and Hohl, {Raymond J.}",

note = "Funding Information: This work was supported by a Translational Research Grant from the Leukemia Society of America, the Roy J. Carver Charitable Trust as a Research Program of Excellence, the Roland W. Holden Family Program for Experimental Cancer Therapeutics, and the NCI Holden Comprehensive Cancer Center at the University of Iowa. The NCC-RAS-004 antibody was kindly provided by Dr. Setsuo Hirohashi (National Cancer Center Research Institute, Tokyo, Japan). Lovastatin was kindly provided by Alfred Alberts (Merck, Sharp and Dohme, Darmstadt, Germany). ",

year = "2005",

month = may,

doi = "10.1016/j.leukres.2004.10.007",

language = "English (US)",

volume = "29",

pages = "527--533",

journal = "Leukemia Research",

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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.

N1 - Funding Information: This work was supported by a Translational Research Grant from the Leukemia Society of America, the Roy J. Carver Charitable Trust as a Research Program of Excellence, the Roland W. Holden Family Program for Experimental Cancer Therapeutics, and the NCI Holden Comprehensive Cancer Center at the University of Iowa. The NCC-RAS-004 antibody was kindly provided by Dr. Setsuo Hirohashi (National Cancer Center Research Institute, Tokyo, Japan). Lovastatin was kindly provided by Alfred Alberts (Merck, Sharp and Dohme, Darmstadt, Germany).

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.

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SN - 0145-2126

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SP - 527

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JO - Leukemia Research

JF - Leukemia Research

IS - 5

ER -

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

Abstract

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