Linked Life Data

11426618

Source:http://linkedlifedata.com/resource/pubmed/id/11426618

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2001-6-27
pubmed:abstractText
We recently identified HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, as a potential therapeutic target of various retinoic acid responsive cancers. Lovastatin, a competitive inhibitor of HMG-CoA reductase, induced a retinoic acid-like differentiation response followed by extensive apoptosis in neuroblastoma cell lines at relatively low concentrations (<20 microM) of this agent. More recently, we demonstrated that acute myeloid leukemias but not acute lymphocytic leukemias also displayed increased sensitivity to lovastatin-induced apoptosis. In this study, we examined the ability of lovastatin to induce differentiation of acute myeloid leukemic cells and to evaluate the role differentiation may hold in the anti-leukemic properties of this agent. Increased expression of the leukocyte integrins CD11b and CD18 as well as down-regulation of the anti-apoptotic gene bcl-2 are associated with late stage differentiation of the myeloid lineage and retinoic acid induced maturation of acute myeloid leukemic cells. Lovastatin exposure induced increased expression of CD11b and CD18 markers similar to retinoic acid treatment. Following 24 hrs exposure to 20 microM lovastatin, all 7 acute myeloid leukemia cell lines tested showed a decrease in bcl-2 mRNA expression while only 1/5 acute lymphocytic leukemia cell lines showed a similar response. A role for bcl-2 in the apoptotic response of acute myeloid leukemia cells to lovastatin was demonstrated as exogenous constitutive expression of bcl-2 in the AML-5 cell line inhibited apoptosis in a time and dose dependent manner. Thus, lovastatin exposure of acute myeloid leukemia cells induced a differentiation response that may contribute to the therapeutic potential of this agent in the treatment of this disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1042-8194
pubmed:author
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
167-78
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Lovastatin induces a pronounced differentiation response in acute myeloid leukemias.
pubmed:affiliation
Department of Cellular and Molecular Biology, Ontario Cancer Institute, University Health Network, Toronto, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't