Shotgun Proteomics and Quantitative Pathway Analysis Study of the Mechanisms of Action of Dehydroeffusol, a Bioactive Phyto-chemical in Medulla Junci with Anti-cancer Activity

ABSTRACT: Dehydroeffusol (DHE) is a rare compound of phenanthrene class isolated from Medulla Junci used in Traditional Chinese herbal medicines. Initial biological evaluation of this compound reveals in vitro and in vivo anticancer ac-tivities. We performed a shotgun proteomic analysis using Orbitrap 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-B, 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. Furthermore, based on the pathway analysis as well as chemical similarity, DHE is predicted to be a phytoestrogen. Our predictions derived from proteomic, bio-informatic and chemoinformatic analyses were validated with individual cell-based experiments. In addition to elucidating the major mechanisms of action of DHE, our study demonstrates an effective workflow for identifying the mechanisms of action of bioactive compounds through shotgun proteomic analysis.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Yi Man Eva Fung  

LAB HEAD: Chi-Ming Che

PROVIDER: PXD009389 | Pride | 2018-06-05

REPOSITORIES: Pride