Document Detail


Proteomic analysis of covalent modifications of tubulins by isothiocyanates.
MedLine Citation:
PMID:  22649267     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Zhen Xiao; Lixin Mi; Fung-Lung Chung; Timothy D Veenstra
Related Documents :
3417357 - Biochemistry of the cell surface of listeria strains: a locating general view.
22451657 - Engulfment protein gulp is regulator of transforming growth factor-β response in ovari...
19376917 - Coaggregation by the freshwater bacterium sphingomonas natatoria alters dual-species bi...
22406527 - Short-term studies using ceramic scaffolds in lapine model for osteochondral defect ame...
11537977 - The role of a cell surface inhibitor in early signal transduction associated with the r...
23770217 - Response to fish specific reproductive hormones and endocrine disrupting chemicals of a...
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    
Affiliation:
Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / 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:
R01 CA100853/CA/NCI NIH HHS
Chemical
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
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease,...
Next Document:  Contribution of CoA ligases to benzenoid biosynthesis in petunia flowers.