Armillaria ostoyae extracts inhibit EMT of cancer cell lines via TGF-β and Wnt/β-catenin signaling components

• Published in: Food bioscience 2024-02, Vol.57, p.103250, Article 103250
• Main Authors: Jovanović, Milena, Virijević, Katarina, Grujović, Mirjana, Ćirić, Andrija, Petrović, Ivica, Arsenijević, Dejan, Živanović, Marko, Ljujić, Biljana, Šeklić, Dragana
• Format: Article
• Language: English
• Subjects: adenocarcinoma; Armillaria ostoyae; cadherins; cell movement; colorectal neoplasms; ethanol; ethyl ether; flow cytometry; fluorescent antibody technique; Fungotherapy; genes; human nutrition; metastasis; Migration; mushrooms; naringin; neoplasm cells; Phenolics; protein content; rutin; Sinapic acid; Smad2; uterine cervical neoplasms; vimentin
• ISSN: 2212-4292; 2212-4306
• DOI: 10.1016/j.fbio.2023.103250

Armillaria ostoyae is an edible mushroom, appreciated in human nutrition, with several medicinal properties already proven. However, its phenolic composition and effects on cancer have never been investigated so far, especially regarding specific signaling pathways included in first steps of cancer metastatic process, epithelial-mesenchymal transition (EMT) and migration. We report phenolic profile of two Armillaria ostoyae extracts, ethanol and diethyl ether (E and DE) and their effects on colorectal carcinoma (HCT-116) and cervical adenocarcinoma (HeLa) cells. Phenolics were detected using HPLC, while effects on cancer cells were investigated using MTT test; expression of markers related to EMT on gene and protein level by flow cytometry, immunofluorescence and qRT-PCR method. Antimigratory potential was assessed on collective and individual type of migration by Wound healing assay and RTCA technique. Sinapic acid was detected as the main phenolic component in E, while rutin and naringin were dominant in DE type of extract. Extracts notably suppressed pro-EMT markers: vimentin, N-cadherin, β-catenin, Snail, Smad2 and MMP-9, and elevated anti-EMT marker E-cadherin. Consequently, collective and single cell migration were significantly inhibited via regulation of TGF-β and Wnt/β-catenin signaling components. DE extract was more efficient in suppression of EMT and migration of colorectal and cervical cancer cells. [Display omitted] •First report on A. ostoyae mushroom extracts on cancer cells.•Diethyl ether and ethanolic extracts had anti-EMT effect on cancer cells.•Molecular mechanism of action via regulation of TGF-β and Wnt signaling pathways.•Colorectal cancer HCT-116 cells were more sensitive to applied extracts.•A. ostoyae, novel, promising and noteworthy natural source of biological activity.