Potential Effect of <i>Pseudevernia furfuracea</i> (L.) Zopf Extract and Metabolite Physodic Acid on Tumour Microenvironment Modulation in MCF-10A Cells
Klaudia Petrova,
Martin Kello,
Tomas Kuruc,
Miriam Backorova,
Eva Petrovova,
Maria Vilkova,
Michal Goga,
Dajana Rucova,
Martin Backor,
Jan Mojzis
Affiliations
Klaudia Petrova
Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
Martin Kello
Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
Tomas Kuruc
Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
Miriam Backorova
Department of Pharmaceutical Technology, Pharmacognosy and Botany, University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovakia
Eva Petrovova
Department of Anatomy, Histology and Physiology, University of Veterinary Medicine and Pharmacy, 041 81 Košice, Slovakia
Maria Vilkova
Department of NMR Spectroscopy, Institute of Chemistry, Faculty of Science, Pavol Jozef Šafárik University, Moyzesova 11, 040 11 Košice, Slovakia
Michal Goga
Core Facility Cell Imaging and Ultrastructure Research, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria
Dajana Rucova
Department of Botany, Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University, Mánesova 23, 041 67 Košice, Slovakia
Martin Backor
Department of Botany, Institute of Biology and Ecology, Faculty of Science, Pavol Jozef Šafárik University, Mánesova 23, 041 67 Košice, Slovakia
Jan Mojzis
Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, 040 01 Košice, Slovakia
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 Pseudevernia furfuracea (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 ex ovo 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.
