Pharmaceutical Sciences Faculty Publications

Title

Identification of Potential Protein Targets of Isothiocyanates by Proteomics

Document Type

Article

Publication Date

10-17-2011

Journal Title

Chemical Research in Toxicology

ISSN

1520-5010

Volume

24

Issue

10

First Page

1735

Last Page

1743

DOI

10.1021/tx2002806

PubMed ID

21838287

PubMed Central® ID

PMC3493163

Abstract

Isothiocyanates (ITCs), such as phenethyl isothiocyanate (PEITC) and sulforaphane (SFN), are effective cancer chemopreventive compounds. It is believed that the major mechanism for the cancer preventive activity of ITCs is through the induction of cell cycle arrest and apoptosis. However, the upstream molecular targets of ITCs have been underexplored until recently. To identify proteins that are covalently modified by ITCs, human non-small cell lung cancer A549 cells were treated with (14)C-PEITC and (14)C-SFN, and the cell lysates were extracted for analysis by 2-D gel electrophoresis and mass spectrometry. After superimposing the colloidal Coomassie blue protein staining pattern with the pattern of radioactivity obtained from X-ray films, it was clear that only a small fraction of cellular proteins contained radioactivity, presumably resulting from selective binding with PEITC or SFN via thiocarbamation. More than 30 proteins with a variety of biological functions were identified with high confidence. Here, we report the identities of these potential ITC target proteins and discuss their biological relevance. The discovery of the protein targets may facilitate studies of the mechanisms by which ITCs exert their cancer preventive activity and provide the molecular basis for designing more efficacious ITC compounds.

Keywords

Anticarcinogenic agents, apoptosis, tumor, chromatography, proteomics, spectrometry

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