| Proteomic analysis of covalent modifications of tubulins by isothiocyanates. | |
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MedLine Citation:
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PMID: 22649267 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although isothiocyanates (ITC), which are found in cruciferous vegetables, have been shown to inhibit carcinogenesis in animal models and induce apoptosis and cell cycle arrest in tumor cells, the biochemical mechanisms of cell growth inhibition by these compounds are not fully understood. Studies have reported that ITC binding to intracellular proteins may be an important event for initiating apoptosis. Specific protein target(s) and molecular mechanisms for ITC have been investigated in human lung cancer A549 cells using proteomic tools. Cells were treated with various amounts (1-100 μmol/L) of radiolabeled phenethyl-ITC (PEITC) and sulforaphane (SFN) and the extracted proteins resolved using 2-dimensional gel electrophoresis. The results of mass spectrometric analyses suggested that tubulin may be an in vivo binding target for ITC. The binding of ITC to tubulin was associated with growth arrest. The proliferation of A549 cells was significantly reduced by ITC, with benzyl-ITC (BITC) having a greater relative activity than PEITC or SFN. Mitotic arrest and apoptosis as well as disruption of microtubule polymerization were induced in the order: BITC > PEITC > SFN. An analysis of tubulins isolated from BITC-treated A549 cells showed that Cys(347), a conserved cysteine in all α-tubulin isoforms, was covalently modified by BITC. Taken together, these results suggest that tubulin is a binding target of ITC and that this interaction can lead to growth inhibition and apoptosis. |
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Authors:
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Zhen Xiao; Lixin Mi; Fung-Lung Chung; Timothy D Veenstra |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-05-30 |
Journal Detail:
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Title: The Journal of nutrition Volume: 142 ISSN: 1541-6100 ISO Abbreviation: J. Nutr. Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-06-21 Completed Date: 2012-08-30 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0404243 Medline TA: J Nutr Country: United States |
Other Details:
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Languages: eng Pagination: 1377S-81S Citation Subset: IM |
Affiliation:
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Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Phytogenic
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pharmacology*,
therapeutic use Apoptosis / drug effects Cell Cycle Checkpoints / drug effects Cell Line, Tumor Cell Proliferation / drug effects Cysteine / metabolism Diet Electrophoresis, Gel, Two-Dimensional Humans Isothiocyanates / pharmacology*, therapeutic use Lung Neoplasms / drug therapy*, metabolism Mass Spectrometry Microtubules / drug effects Mitosis / drug effects Phytotherapy* Plant Extracts / pharmacology, therapeutic use Protein Binding Protein Isoforms Proteomics Tubulin / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA100853/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/Isothiocyanates; 0/Plant Extracts; 0/Protein Isoforms; 0/Tubulin; 52-90-4/Cysteine; 6U7TFK75KV/phenethyl isothiocyanate; 871J6YOR8Q/benzyl isothiocyanate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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