Shotgun Proteomics and Quantitative Pathway Analysis of the Mechanisms of Action of Dehydroeffusol, a Bioactive Phytochemical with Anticancer Activity from Juncus effusus.
I-Sheng ChangLai-King SyBei CaoChing Tung LumWai-Lun KwongYi-Man Eva FungChun-Nam LokChi-Ming ChePublished in: Journal of proteome research (2018)
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.
Keyphrases
- endoplasmic reticulum stress
- signaling pathway
- induced apoptosis
- liquid chromatography tandem mass spectrometry
- transcription factor
- label free
- mass spectrometry
- epithelial mesenchymal transition
- high resolution
- simultaneous determination
- oxidative stress
- lymph node
- cell death
- cell therapy
- stem cells
- solid phase extraction
- big data
- nuclear factor
- toll like receptor
- dna binding
- bone marrow
- protein kinase
- mesenchymal stem cells
- machine learning
- tyrosine kinase
- amino acid
- cell wall