Shotgun Proteomics and Quantitative Pathway Analysis of the Mechanisms of Action of Dehydroeffusol, a Bioactive Phytochemical with Anticancer Activity from Juncus effusus.

Abstract:

:Dehydroeffusol (DHE) is a phenanthrene isolated from the Chinese medicinal plant Juncus effusus. Biological evaluation of DHE reveals in vitro and in vivo anticancer effects. We performed a shotgun proteomic analysis using liquid chromatography-tandem mass spectrometry to investigate the changes in the protein profiles in cancer cells upon DHE treatment. DHE affected cancer-associated signaling pathways, including NF-κB, β-catenin, and endoplasmic reticulum stress. Through quantitative pathway and key node analysis of the proteomics data, activating transcription factor 2 (ATF-2) and c-Jun kinase (JNK) were found to be the key components in DHE's modulated biological pathways. Based on the pathway analysis as well as chemical similarity to estradiol, DHE is proposed to be a phytoestrogen. The proteomic, bioinformatic, and chemoinformatic analyses were further verified with individual cell-based experiments. Our study demonstrates a workflow for identifying the mechanisms of action of DHE through shotgun proteomic analysis.

journal_name

J Proteome Res

authors

Chang IS,Sy LK,Cao B,Lum CT,Kwong WL,Fung YE,Lok CN,Che CM

doi

10.1021/acs.jproteome.8b00227

subject

Has Abstract

pub_date

2018-07-06 00:00:00

pages

2470-2479

issue

7

eissn

1535-3893

issn

1535-3907

journal_volume

17

pub_type

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