| pubmed-article:15450939 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15450939 | lifeskim:mentions | umls-concept:C1516334 | lld:lifeskim |
| pubmed-article:15450939 | lifeskim:mentions | umls-concept:C1512505 | lld:lifeskim |
| pubmed-article:15450939 | lifeskim:mentions | umls-concept:C0596290 | lld:lifeskim |
| pubmed-article:15450939 | lifeskim:mentions | umls-concept:C1533646 | lld:lifeskim |
| pubmed-article:15450939 | lifeskim:mentions | umls-concept:C0441655 | lld:lifeskim |
| pubmed-article:15450939 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:15450939 | lifeskim:mentions | umls-concept:C2248143 | lld:lifeskim |
| pubmed-article:15450939 | lifeskim:mentions | umls-concept:C0061223 | lld:lifeskim |
| pubmed-article:15450939 | lifeskim:mentions | umls-concept:C0053463 | lld:lifeskim |
| pubmed-article:15450939 | lifeskim:mentions | umls-concept:C0332291 | lld:lifeskim |
| pubmed-article:15450939 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:15450939 | pubmed:dateCreated | 2004-9-28 | lld:pubmed |
| pubmed-article:15450939 | 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. | lld:pubmed |
| pubmed-article:15450939 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15450939 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15450939 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15450939 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15450939 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:15450939 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15450939 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:15450939 | pubmed:issn | 0006-2952 | lld:pubmed |
| pubmed-article:15450939 | pubmed:author | pubmed-author:ArcherMichael... | lld:pubmed |
| pubmed-article:15450939 | pubmed:author | pubmed-author:El-SohemyAhme... | lld:pubmed |
| pubmed-article:15450939 | pubmed:author | pubmed-author:DuncanRobin... | lld:pubmed |
| pubmed-article:15450939 | pubmed:author | pubmed-author:LauDominicD | lld:pubmed |
| pubmed-article:15450939 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15450939 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:15450939 | pubmed:volume | 68 | lld:pubmed |
| pubmed-article:15450939 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15450939 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15450939 | pubmed:pagination | 1739-47 | lld:pubmed |
| pubmed-article:15450939 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:15450939 | pubmed:meshHeading | pubmed-meshheading:15450939... | lld:pubmed |
| pubmed-article:15450939 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15450939 | 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. | lld:pubmed |
| pubmed-article:15450939 | pubmed:affiliation | Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Fitzgerald Building, 150 College Street, Toronto, Ont., Canada M5S 3E2. | lld:pubmed |
| pubmed-article:15450939 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15450939 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:15450939 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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