| Gamma-tocotrienol induced apoptosis is associated with unfolded protein response in human breast cancer cells. | |
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MedLine Citation:
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PMID: 21429729 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Gamma-tocotrienol (γ-T3) is a member of the vitamin E family. Tocotrienols (T3s) are powerful antioxidants and possess anticancer, neuroprotective and cholesterol-lowering properties. Tocotrienols inhibit the growth of various cancer cell lines without affecting normal cells. Less is known about the exact mechanisms of action of T3s on cell death and other growth inhibitory pathways. In the present study, we demonstrate that γ-T3 induces apoptosis in MDA-MB 231 and MCF-7 breast cancer cells as evident by PARP cleavage and caspase-7 activation. Gene expression analysis of MCF-7 cells treated with γ-T3 revealed alterations in the expression of multiple genes involved in cell growth and proliferation, cell death, cell cycle, cellular development, cellular movement and gene expression. Further analysis of differentially modulated genes using Ingenuity Pathway Analysis software suggested modulation of canonical signal transduction or metabolic pathways such as NRF-2-mediated oxidative stress response, TGF-β signaling and endoplasmic reticulum (ER) stress response. Analysis of ER-stress-related proteins in MCF-7 and MDA-MB 231 cells treated with γ-T3 demonstrated activation of PERK and pIRE1α pathway to induce ER stress. Activating transcription factor 3 (ATF3) was identified as the most up-regulated gene (16.8-fold) in response to γ-T3. Activating transcription factor 3 knockdown using siRNA suggested an essential role of ATF3 in γ-T3-induced apoptosis. In summary, we demonstrate that γ-T3 modulates ER stress signaling and have identified ATF3 as a molecular target for γ-T3 in breast cancer cells. |
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Authors:
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Dorrelyn Patacsil; Anh Thu Tran; Youn Sook Cho; Simeng Suy; Francisco Saenz; Irina Malyukova; Habtom Ressom; Sean P Collins; Robert Clarke; Deepak Kumar |
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Publication Detail:
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Type: Journal Article Date: 2011-03-22 |
Journal Detail:
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Title: The Journal of nutritional biochemistry Volume: 23 ISSN: 1873-4847 ISO Abbreviation: J. Nutr. Biochem. Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2011-12-14 Completed Date: 2012-06-19 Revised Date: 2013-02-20 |
Medline Journal Info:
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Nlm Unique ID: 9010081 Medline TA: J Nutr Biochem Country: United States |
Other Details:
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Languages: eng Pagination: 93-100 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Cancer Research Laboratory, Department of Biological and Environmental Sciences, University of the District of Columbia, Washington, DC 20008, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Activating Transcription Factor 3
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genetics,
metabolism Apoptosis / drug effects Breast Neoplasms / drug therapy*, genetics, metabolism, pathology* Caspase 7 / metabolism Cell Cycle / drug effects, genetics Cell Death / drug effects, genetics Cell Line, Tumor Cell Proliferation / drug effects Chromans / pharmacology* Endoplasmic Reticulum Stress Female Gene Expression Regulation, Neoplastic / drug effects Humans NF-E2-Related Factor 2 / genetics, metabolism Poly(ADP-ribose) Polymerases / metabolism Signal Transduction Unfolded Protein Response / drug effects* Vitamin E / analogs & derivatives*, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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SC1 CA141935-01/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/ATF3 protein, human; 0/Activating Transcription Factor 3; 0/Chromans; 0/NF-E2-Related Factor 2; 0/NFE2L2 protein, human; 1406-18-4/Vitamin E; 4382-43-8/plastochromanol 8; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspase 7 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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