| 2-methoxyestradiol-induced cell death in osteosarcoma cells is preceded by cell cycle arrest. | |
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MedLine Citation:
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PMID: 18384113 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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2-Methoxyestradiol (2-ME), a naturally occurring mammalian metabolite of 17beta-Estradiol (E2), induces cell death in osteosarcoma cells. To further understand the molecular mechanisms of action, we have investigated cell cycle progression in 2-ME-treated human osteosarcoma (MG63, SaOS-2 and LM7 [corrected]) cells. At 5 microM, 2-ME induced growth arrest by inducing a block in cell cycle; 2-ME-treatment resulted in 2-fold increases in G1 phase cells and a decrease in S phase cells in MG63 and SaOS-2 osteosarcoma cell lines, compared to the appropriate vehicle controls. 2-ME-treatment induced a threefold increase in the G2 phase in LM7 [corrected] osteosarcoma cells. The results demonstrated steroid specificity, as the tumorigenic metabolite, 16alpha-hydroxyestradiol (16-OHE), did not have any effect on cell cycle progression in osteosarcoma cells. The cell cycle arrest coincided with an increase in expression of the cell cycle markers p21, p27 and p53 proteins in 2-ME-treated osteosarcoma cells. Also, MG63 cells, transiently transfected with cDNA for a 'loss of function mutant' RNA-dependent protein kinase (PKR) protein, were resistant to 2-ME-induced cell cycle arrest. These results suggest that 2-ME works in concert with factors regulating cell cycle progression, and cell cycle arrest precedes cell death in 2-ME-treated osteosarcoma cells. |
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Authors:
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Avudaiappan Maran; Kristen L Shogren; Michaela Benedikt; Gobinda Sarkar; Russell T Turner; Michael J Yaszemski |
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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 |
Journal Detail:
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Title: Journal of cellular biochemistry Volume: 104 ISSN: 1097-4644 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2008 Aug |
Date Detail:
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Created Date: 2008-07-28 Completed Date: 2008-10-17 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: United States |
Other Details:
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Languages: eng Pagination: 1937-45 Citation Subset: IM |
Affiliation:
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Department of Orthopedics, Mayo Clinic, Rochester, Minnesota 55905, USA. maran@mayo.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cell Cycle
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drug effects* Cell Cycle Proteins / metabolism Cell Death / drug effects Cell Line, Tumor Cell Proliferation / drug effects Cyclin-Dependent Kinase Inhibitor p21 / metabolism Estradiol / analogs & derivatives*, pharmacology Flow Cytometry Genes, Dominant Humans Ligands Mutant Proteins / metabolism Osteosarcoma / enzymology, pathology* eIF-2 Kinase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AR047974/AR/NIAMS NIH HHS; CA10287801/CA/NCI NIH HHS; R01 AA011140-09/AA/NIAAA NIH HHS; R01 AR047974-05/AR/NIAMS NIH HHS; R03 CA102878-02/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Ligands; 0/Mutant Proteins; 362-07-2/2-methoxyestradiol; 50-28-2/Estradiol; EC 2.7.11.1/eIF-2 Kinase |
| Comments/Corrections | |
Erratum In:
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J Cell Biochem. 2008 Nov 1;105(4):1146 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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