Lichens produce various unique chemicals that are used in the pharmaceutical industry. To screen for novel lichen secondary metabolites that inhibit the stemness potential of colorectal cancer cells, we tested acetone extracts of 11 lichen samples collected in Chile. Tumidulin, isolated from Niebla sp., reduced spheroid formation in CSC221, DLD1, and HT29 cells. In addition, mRNA expressions and protein levels of cancer stem markers aldehyde dehydrogenase-1 (ALDH1), cluster of differentiation 133 (CD133), CD44, Lgr5, and Musashi-1 were reduced after tumidulin treatment. Tumidulin decreased the transcriptional activity of the glioma-associated oncogene homolog zinc finger protein (Gli) promoter in reporter assays, and western blotting confirmed decreased Gli1, Gli2, and Smoothened (SMO) protein levels. Moreover, the tumidulin activity was not observed in the presence of Gli and SMO inhibitors. Together, these results demonstrate for the first time that tumidulin is a potent inhibitor of colorectal cancer cell stemness.

Secondary metabolites of lichens are promising bioresources for candidate anti-cancer drugs. Accordingly, several approaches have been proposed for screening these molecules for novel anti-cancer lead compounds. In this study, we found that a non-toxic concentration of physciosporin, a compound isolated from Pseudocyphellaria granulata, significantly decreased colony formation on soft agar and spheroid formation by CSC221 cancer stem-like cells. Physciosporin also decreased spheroid formation in other colorectal cancer cell lines, including DLD1, Caco2, and HT29. Aldehyde dehydrogenase-1 (ALDH1), the most important cancer stem marker, was sharply downregulated at both the protein and mRNA level following treatment with physciosporin. Physciosporin also decreased the transcriptional activity of the glioma-associated oncogene homolog zinc finger protein (Gli), as well as the Hes1 and CSL promoters, in reporter assays. Moreover, the drug significantly suppressed spheroid formation in CSC221 cells overexpressing Gli1/2 or ΔEN1 (an S2-cleaved but membrane-tethered form of human Notch1) but did not suppress spheroid formation in cells overexpressing both Gli1/2 and ∆EN1, suggesting that physciosporin suppresses colon cancer cell stemness through the Sonic hedgehog and Notch signaling pathways. Together, these results demonstrate for the first time that physciosporin is a potent inhibitor of colorectal cancer cell stemness.

The influence of the pH of the bark of two tree species belonging at Nothofagus genus on the lichen and bryophyte richness was studied. The tree species considered for this study were: N. dombeyi and N. macracarpa situated in two pre-Andean localities; one in the "Radal Siete Tazas" National Reserve and the other in the "Altos de Lircay" National Reserve, Central Chile. In each locality, a total of 20 phorophytes were examined: 10 N. dombeyi and 10 N. obliqua. In each phorophyte, the total lichens and bryophytes were inventoried, the diameter of each one of the phorophytes was measured at breast height (DHA) and, in addition, 10 g of bark were extracted in order to check the pH. The pH of the bark was determined by means of the Mezger’s method (1996) and afterwards related to the lichen and bryophyte richness found in the phorophytes of each tree species sampled in both localities. In both localities, the pH of bark of the N. dombeyi phorophytes was markedly more acidic than the one of the N. obliqua. Statistical analyses show a significant difference between the pH of one species and other. The pH of the barks of N. dombeyi and N. obliqua phorophytes, in both localities, not correlated with the richness of the different groups (lichens, mosses and liverworts). However, according to the inventories carried, it observed that some species of lichens have a close relation with the pH of the bark of one or other of the two tree species studied and only a low percentage of them were indifferent to pH of the phorophytes. The mosses preferred bark with pH near to neutrality such as those of N. obliqua, while the liverworts preferred bark were more acid, such as the ones of N. dombeyi.

Lichens are an important source of diverse and unique secondary metabolites with recognized biological activities through experimental and computational procedures. The objective of this study is to investigate the metabolomic profile of the ethanolic extract of the Antarctic lichen Gondwania regalis and evaluate its antioxidant and antidiabetic activities with in vitro, in silico, and molecular dynamics simulations. Twenty-one compounds were tentatively identified for the first time using UHPLC/ESI/QToF/MS in negative mode. For antioxidant activity, the DPPH assay showed an IC₅₀ value of 2246.149 µg/mL; the total phenolic content was 31.9 mg GAE/g, the ORAC assay was 13.463 µmol Trolox/g, and the FRAP assay revealed 6.802 µmol Trolox/g. Regarding antidiabetic activity, enzyme inhibition yielded IC₅₀ values of 326.4513 µg/mL for pancreatic lipase, 19.49 µg/mL for α-glucosidase, and 585.216 µg/mL for α-amylase. Molecular docking identified sekikaic acid as the most promising compound, with strong binding affinities to catalytic sites, while molecular dynamics confirmed its stability and interactions. Toxicological and pharmacokinetic analyses supported its drug-like potential without significant risks. These findings suggest that the ethanolic extract of Gondwania regalis is a promising source of bioactive compounds for developing natural antioxidant and antidiabetic therapies.

The richness, composition, abundance, and correlation with the atmospheric oxide concentrations of the community of corticolous lichens in the urban and peri-urban areas of the city of Ibagué (Colombia) were evaluated, selecting 25 individuals of the four most abundant phorophyte species. Twenty-nine lichen taxa grouped in 13 families and 17 genera were recorded, with a higher lichen coverage and taxa richness in the urban area. A non-metric multidimensional scaling (NMDS) analysis showed the conformation of two lichen communities associated with the urban and peri-urban areas of the city, and variation in composition among the phorophyte species. Exclusive and indicator taxa were found for both zones, as well as associations between variables through the application of a general linear model. Higher concentrations of atmospheric gases CO, SO₂, NO₂, and O₃ were found in the urban zone, and positive/negative relationships with some lichen taxa. There is high variability in the response of the lichen assemblage of urban and peri-urban ecosystems to environmental effects, with substantial or minimal changes in the variables of richness, coverage, and phorophyte association, and according to their interaction with atmospheric oxides, the patterns of potential tolerant and/or sensitive species are formed for their implementation in bioindication studies.