Cellular Target Proteome in Breast Cancer Cells of an Oplopane Sesquiterpenoid Isolated fromTussilago farfara

Abstract

Tussilago farfara 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 from T. farfara using quantitative chemical proteomics in MDA-MB-231 and MCF-7 human breast cancer cells. Compound 8, 7β-(3′-ethyl-cis-crotonoyloxy)-1α-(2′-methyl butyryloxy)-3,14-dehydro-Z-notonipetranone, exhibited potent antiproliferative activity based on its α,β-unsaturated carbonyl moiety, and its potential cellular target proteins were identified using a compound 8-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 the α,β-unsaturated carbonyl moiety of compound 8 and 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 compound 8 in breast cancer cells, identification of potential target proteins contributes to enhanced understanding of its antiproliferative and anti-inflammatory effects.

A Comparative Analysis of the Anatomy, Phenolic Profile, and Antioxidant Capacity of Tussilago farfara L. Vegetative Organs

“…In colorectal cancer, they show an antitumorigenic and anti-inflammatory effect via NF-κB, Nrf2, Wnt, and β-catenin pathways modulation [55][56][57] and induce cytotoxicity in HT-29 colorectal cancer cells in a dose-dependent manner [58]. In breast cancer, isolated T. farfara sesquiterpenoids exert an antiproliferative activity by interacting with cysteine residues of proteins [59]. In hepatic carcinoma, the methanolic extract of leaves induces apoptosis in Huh7 cells by activating the TRAIL pathway, inhibiting MKK7-TIPRL interaction, and increasing MKK7/JNK phosphorylation [60].…”