Document Detail

Proteomic analysis of covalent modifications of tubulins by isothiocyanates.
MedLine Citation:
PMID:  22649267     Owner:  NLM     Status:  MEDLINE    
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.
Zhen Xiao; Lixin Mi; Fung-Lung Chung; Timothy D Veenstra
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-05-30
Journal Detail:
Title:  The Journal of nutrition     Volume:  142     ISSN:  1541-6100     ISO Abbreviation:  J. Nutr.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-21     Completed Date:  2012-08-30     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  0404243     Medline TA:  J Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1377S-81S     Citation Subset:  IM    
Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD, USA.
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MeSH Terms
Antineoplastic Agents, Phytogenic / pharmacology*,  therapeutic use
Apoptosis / drug effects
Cell Cycle Checkpoints / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cysteine / metabolism
Electrophoresis, Gel, Two-Dimensional
Isothiocyanates / pharmacology*,  therapeutic use
Lung Neoplasms / drug therapy*,  metabolism
Mass Spectrometry
Microtubules / drug effects
Mitosis / drug effects
Plant Extracts / pharmacology,  therapeutic use
Protein Binding
Protein Isoforms
Tubulin / metabolism*
Grant Support
Reg. No./Substance:
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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