Linked Life Data

15450939

Source:http://linkedlifedata.com/resource/pubmed/id/15450939

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2004-9-28
pubmed:abstractText
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyzes the formation of mevalonate, a precursor of cholesterol that is also required for cell proliferation. Mevalonate depletion results in a G1 phase cell cycle arrest that is mediated in part by impaired activity of cyclin-dependent kinase (CDK) 2, and decreased expression of positive regulators of G1 to S phase progression. Inhibition of mevalonate synthesis may, therefore, be a useful strategy to impair the growth of malignant cells. Plant isoprenoids, including beta-ionone and geraniol, have previously been shown to inhibit rodent mammary tumor development, and rodent and avian hepatic HMG-CoA reductase activity. We hypothesized that the putative anti-proliferative and cell cycle inhibitory effects of beta-ionone and geraniol on MCF-7 human breast cancer cells in culture are mediated by mevalonate depletion resulting from inhibition of HMG-CoA reductase activity. Flow cytometric analysis showed a G1 arrest in isoprenoid-treated MCF-7 cells, and also a G2/M arrest at higher concentrations of isoprenoids. These compounds minimally affected the growth of MCF-10F normal breast epithelial cells. Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4, without changing the expression of p21cip1 or p27kip1. Although both beta-ionone and geraniol also inhibited MCF-7 proliferation, only geraniol inhibited HMG-CoA reductase activity. While these effects were significantly correlated (r2=0.89, P <0.01), they were not causally related, since exogenous mevalonate did not restore growth in geraniol-inhibited cells. These findings indicate that mechanisms other than impaired mevalonate synthesis mediate the anti-proliferative and cell cycle regulatory effects of beta-ionone and geraniol in human breast cancer cells.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1739-47
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15450939-Breast Neoplasms, pubmed-meshheading:15450939-CDC2-CDC28 Kinases, pubmed-meshheading:15450939-Cell Cycle, pubmed-meshheading:15450939-Cell Division, pubmed-meshheading:15450939-Cell Proliferation, pubmed-meshheading:15450939-Cyclin-Dependent Kinase 2, pubmed-meshheading:15450939-Dose-Response Relationship, Drug, pubmed-meshheading:15450939-G1 Phase, pubmed-meshheading:15450939-Gene Expression, pubmed-meshheading:15450939-Humans, pubmed-meshheading:15450939-Hydroxymethylglutaryl CoA Reductases, pubmed-meshheading:15450939-Hydroxymethylglutaryl-CoA Reductase Inhibitors, pubmed-meshheading:15450939-Norisoprenoids, pubmed-meshheading:15450939-S Phase, pubmed-meshheading:15450939-Terpenes, pubmed-meshheading:15450939-Time Factors, pubmed-meshheading:15450939-Tumor Cells, Cultured
pubmed:year
2004
pubmed:articleTitle
Geraniol and beta-ionone inhibit proliferation, cell cycle progression, and cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of effects on HMG-CoA reductase activity.
pubmed:affiliation
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Fitzgerald Building, 150 College Street, Toronto, Ont., Canada M5S 3E2.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't