| Anti-proliferative effects of gamma-tocotrienol on mammary tumour cells are associated with suppression of cell cycle progression. | |
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MedLine Citation:
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PMID: 19922488 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: Previous studies have shown that gamma-tocotrienol induces potent anti-proliferative effects on +SA mammary tumour cells in culture; here, investigations have been conducted to determine its effects on intracellular signalling proteins involved in regulating cell cycle progression. MATERIALS AND METHODS: +SA cells were maintained in mitogen-free defined media containing 0 or 4 micromgamma-tocotrienol, for 48 h to synchronize cell cycle in G(0) phase, and then they were exposed to 100 ng/ml EGF to initiate cell cycle progression. Whole cell lysates were collected at various time points from each treatment group and were prepared for Western blot analysis. RESULTS AND CONCLUSIONS: Treatment with 4 micromgamma-tocotrienol significantly inhibited +SA cell proliferation over a 4-day culture period. Moreover, this treatment resulted in a relatively large reduction in cyclin D1, cyclin dependent kinase (CDK)4, CDK2 and CDK6 levels, between 4 and 24 h after EGF exposure. Tocotrienol treatment also resulted in a relatively large increase in CDK inhibitor (CKI) p27, prior to and after EGF exposure, but had little effect on levels of CKIs, p21 and p15. Tocotrienol treatment also induced a large relative reduction in retinoblastoma (Rb) protein phosphorylation at ser780 and ser807/811. These findings strongly suggest that anti-proliferative effects of gamma-tocotrienol are associated with reduction in cell cycle progression from G(1) to S, as evidenced by increased p27 levels, and a corresponding decrease in cyclin D1, CDK2, CDK4, CDK6 and phosphorylated Rb levels. |
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Authors:
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G V Samant; V B Wali; P W Sylvester |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-11-17 |
Journal Detail:
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Title: Cell proliferation Volume: 43 ISSN: 1365-2184 ISO Abbreviation: Cell Prolif. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-14 Completed Date: 2010-02-12 Revised Date: 2012-06-25 |
Medline Journal Info:
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Nlm Unique ID: 9105195 Medline TA: Cell Prolif Country: England |
Other Details:
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Languages: eng Pagination: 77-83 Citation Subset: IM |
Affiliation:
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College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle / drug effects* Cell Line Chromans / pharmacology* Cyclin D1 / metabolism Cyclin-Dependent Kinase 2 / metabolism Cyclin-Dependent Kinase 4 / metabolism Cyclin-Dependent Kinase 6 / metabolism Cyclin-Dependent Kinase Inhibitor p27 / metabolism Epidermal Growth Factor / pharmacology Female G0 Phase Mammary Glands, Animal / metabolism Mammary Neoplasms, Experimental / metabolism* Mice Phosphorylation Vitamin E / analogs & derivatives*, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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CA86833/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chromans; 136601-57-5/Cyclin D1; 1406-18-4/Vitamin E; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 4382-43-8/plastochromanol 8; 62229-50-9/Epidermal Growth Factor; EC 2.7.11.22/CDK2 protein, human; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/CDK6 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinase 6 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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