Document Detail


Anti-proliferative effects of gamma-tocotrienol on mammary tumour cells are associated with suppression of cell cycle progression.
MedLine Citation:
PMID:  19922488     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
G V Samant; V B Wali; P W Sylvester
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-11-17
Journal Detail:
Title:  Cell proliferation     Volume:  43     ISSN:  1365-2184     ISO Abbreviation:  Cell Prolif.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-14     Completed Date:  2010-02-12     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  9105195     Medline TA:  Cell Prolif     Country:  England    
Other Details:
Languages:  eng     Pagination:  77-83     Citation Subset:  IM    
Affiliation:
College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
CA86833/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
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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