Food Bioscience ( IF 4.8 ) Pub Date : 2023-10-13 , DOI: 10.1016/j.fbio.2023.103250 Milena Jovanović , Katarina Virijević , Mirjana Grujović , Andrija Ćirić , Ivica Petrović , Marko Živanović , Biljana Ljujić , Dragana Šeklić
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.
中文翻译:
奥氏蜜环菌提取物通过 TGF-β 和 Wnt/β-catenin 信号传导成分抑制癌细胞系的 EMT
奥氏蜜环菌是一种食用菌,在人类营养中备受推崇,其多种药用特性已得到证实。然而,迄今为止,其酚类成分及其对癌症的影响尚未得到研究,特别是关于癌症转移过程、上皮间质转化(EMT)和迁移的第一步中的特定信号通路。我们报告了两种奥氏蜜环菌提取物、乙醇和乙醚( E和DE )的酚谱及其对结直肠癌 (HCT-116) 和宫颈腺癌细胞 (HeLa) 的影响。采用HPLC检测酚类物质,采用MTT试验考察对癌细胞的影响;采用流式细胞术、免疫荧光和qRT-PCR方法检测EMT相关标志物在基因和蛋白水平上的表达情况。通过伤口愈合测定和 RTCA 技术评估集体和个体迁移类型的抗迁移潜力。E中检测到的主要酚类成分是芥子酸,而DE类提取物中的主要酚类成分是芦丁和柚皮苷。提取物显着抑制了促 EMT 标记物:波形蛋白、N-钙粘蛋白、β-连环蛋白、Snail、Smad2 和 MMP-9,并升高了抗 EMT 标记物 E-钙粘蛋白。因此,通过调节 TGF-β 和 Wnt/β-catenin 信号传导成分,集体和单细胞迁移受到显着抑制。 DE提取物更有效地抑制 EMT 以及结直肠癌细胞和宫颈癌细胞的迁移。