Cellular Target Proteome in Breast Cancer Cells of an Oplopane Sesquiterpenoid Isolated from.
J Nat Prod. 2020 Sep 25 ;83(9):2559-2566. Epub 2020 Sep 3. PMID: 32881525
is a traditional herbal medicine used to treat coughs, bronchitis, and asthma. Its bioactive compounds include sesquiterpenoids with anti-inflammatory, antiproliferative, neuroprotective, and other effects. Biochemical studies have highlighted the mechanisms of action, but the investigations of related molecular pathways have not specified direct molecular targets. Therefore, this study profiled cellular target proteins of a sesquiterpenoid isolated fromusing quantitative chemical proteomics in MDA-MB-231 and MCF-7 human breast cancer cells. Compound, 7β-(3'-ethyl--crotonoyloxy)-1α-(2'-methyl butyryloxy)-3,14-dehydro--notonipetranone, exhibited potent antiproliferative activity based on itsα,β-unsaturated carbonyl moiety, and its potential cellular target proteins were identified using a compound-based clickable probe. Among>200 identified proteins, 17 showed enrichment ratios of>3 in both cell lines, while recombinant 14-3-3 protein zeta and peroxiredoxin-1 were verified using isothermic calorimetry and their alkylation sites. Considering the interaction between theα,β-unsaturated carbonyl moiety of compoundand cysteine residues of the proteins, peptides containing Cys25 and Cys94 of 14-3-3 protein zeta and Cys83 of peroxiredoxin-1 were significantly reduced by this sesquiterpene ester. Although the results did not elucidate the effects of compoundin breast cancer cells, identification of potential target proteins contributes to enhanced understanding of its antiproliferative and anti-inflammatory effects.