Potential Effect of Pseudevernia furfuracea (L.) Zopf Extract and Metabolite Physodic Acid on Tumour Microenvironment Modulation in MCF-10A Cells.
Klaudia PetrovaMartin KelloTomas KurucMiriam BackorovaEva PetrovovaMaria VilkovaMichal GogaDajana RucovaMartin BackorJan MojzisPublished in: Biomolecules (2021)
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.
Keyphrases
- transforming growth factor
- epithelial mesenchymal transition
- induced apoptosis
- signaling pathway
- flow cytometry
- stem cells
- cancer therapy
- cell cycle arrest
- oxidative stress
- endothelial cells
- ms ms
- breast cancer cells
- randomized controlled trial
- systematic review
- drug delivery
- endoplasmic reticulum stress
- vascular endothelial growth factor
- cell death
- bone marrow
- human health
- anti inflammatory
- high speed
- cell proliferation
- optical coherence tomography