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（L.）Zopf 提取物及其代谢产物 Physodic 酸对 MCF-10A 细胞肿瘤微环境调节的潜在作用。

Potential Effect of (L.) Zopf Extract and Metabolite Physodic Acid on Tumour Microenvironment Modulation in MCF-10A Cells.

机构信息

Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia.

Department of Pharmaceutical Technology, Pharmacognosy and Botany, University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovakia.

出版信息

Biomolecules. 2021 Mar 12;11(3):420. doi: 10.3390/biom11030420.

DOI:10.3390/biom11030420
PMID:33809098
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8000760/
Abstract

Lichens comprise a number of unique secondary metabolites with remarkable biological activities and have become an interesting research topic for cancer therapy. However, only a few of these metabolites have been assessed for their effectiveness against various in vitro models. Therefore, the aim of the present study was to assess the effect of extract (L.) Zopf (PSE) and its metabolite physodic acid (Phy) on tumour microenvironment (TME) modulation, focusing on epithelial-mesenchymal transition (EMT), cancer-associated fibroblasts (CAFs) transformation and angiogenesis. Here, we demonstrate, by using flow cytometry, Western blot and immunofluorescence microscopy, that tested compounds inhibited the EMT process in MCF-10A breast cells through decreasing the level of different mesenchymal markers in a time- and dose-dependent manner. By the same mechanisms, PSE and Phy suppressed the function of Transforming growth factor beta (TGF-β)-stimulated fibroblasts. Moreover, PSE and Phy resulted in a decreasing level of the TGF-β canonical pathway Smad2/3, which is essential for tumour growth. Furthermore, PSE and Phy inhibited angiogenesis in a quail embryo chorioallantoic model, which indicates their potential anti-angiogenic activity. These results also provided the first evidence of the modulation of TME by these substances.

摘要

地衣包含许多具有显著生物活性的独特次生代谢物，已成为癌症治疗的一个有趣的研究课题。然而，这些代谢物中只有少数几种已被评估用于治疗各种体外模型的有效性。因此，本研究旨在评估提取物（L.）Zopf（PSE）及其代谢产物 physodic acid（Phy）对肿瘤微环境（TME）调节的影响，重点关注上皮-间充质转化（EMT）、癌症相关成纤维细胞（CAFs）转化和血管生成。在这里，我们通过流式细胞术、Western blot 和免疫荧光显微镜证明，测试化合物通过降低不同间充质标志物的水平，以时间和剂量依赖的方式抑制 MCF-10A 乳腺细胞中的 EMT 过程。通过相同的机制，PSE 和 Phy 抑制了转化生长因子β（TGF-β）刺激的成纤维细胞的功能。此外，PSE 和 Phy 导致 TGF-β 经典途径 Smad2/3 的水平降低，这对肿瘤生长至关重要。此外，PSE 和 Phy 抑制了鹌鹑胚胎绒毛尿囊膜模型中的血管生成，这表明它们具有潜在的抗血管生成活性。这些结果还首次提供了这些物质对 TME 调节的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/71bc85bb7735/biomolecules-11-00420-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/a0e6341fae37/biomolecules-11-00420-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/402e2a685321/biomolecules-11-00420-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/1160fb05823b/biomolecules-11-00420-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/5911fe664038/biomolecules-11-00420-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/73f93abd6083/biomolecules-11-00420-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/d69d506306c8/biomolecules-11-00420-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/ee0a14a28e54/biomolecules-11-00420-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/7886d69432d8/biomolecules-11-00420-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/e8726e307826/biomolecules-11-00420-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/71bc85bb7735/biomolecules-11-00420-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/a0e6341fae37/biomolecules-11-00420-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/402e2a685321/biomolecules-11-00420-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/1160fb05823b/biomolecules-11-00420-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/5911fe664038/biomolecules-11-00420-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/73f93abd6083/biomolecules-11-00420-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/d69d506306c8/biomolecules-11-00420-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/ee0a14a28e54/biomolecules-11-00420-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/7886d69432d8/biomolecules-11-00420-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/e8726e307826/biomolecules-11-00420-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f49b/8000760/71bc85bb7735/biomolecules-11-00420-g010.jpg

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