Abstract
Lichens are a source of secondary metabolites which possess important biological activities, including antioxidant, antibacterial, anti-inflammatory, and cytotoxic effects. The anticancer activity of lichens was shown in many types of tumors, including colorectal cancers (CRC). Several studies revealed that the application of lichen extracts diminished the proliferation of CRC cells and induced apoptosis. Colon carcinogenesis is associated with aberrations in Wnt signaling. Elevated transcriptional activity of β-catenin induces cell survival, proliferation, and migration. Thus, the inhibition of Wnt signaling is a promising therapeutic strategy in colorectal cancer. The aim of this study was the evaluation of the effects of lichen-derived depsides (atranorin, lecanoric acid, squamatic acid) and depsidones (physodic acid, salazinic acid) and a poly-carboxylic fatty acid—caperatic acid, on Wnt signaling in HCT116 and DLD-1 colorectal cancer cell lines. HCT116 cells were more sensitive to the modulatory effects of the compounds. PKF118-310, which was used as a reference β-catenin inhibitor, dose-dependently reduced the expression of the classical β-catenin target gene—Axin2 in both cell lines. Lecanoric acid slightly reduced Axin2 expression in HCT116 cells while caperatic acid tended to reduce Axin2 expression in both cell lines. Physodic acid much more potently decreased Axin2 expression in HCT116 cells than in DLD-1 cells. Physodic acid and caperatic acid also diminished the expression of survivin and MMP7 in a cell line and time-dependent manner. None of the compounds affected the nuclear translocation of β-catenin. This is the first report showing the ability of caperatic acid and physodic acid to modulate β-catenin-dependent transcription.
Highlights
Lichens, which are symbiotic organisms consisting of fungi and photosynthetic partners, are a source of a broad group of unique secondary metabolites, many of which possess important biological activities [1, 2]
The aim of this study was the evaluation of the effects of lichenderived depsides and depsidones and a polycarboxylic fatty acid—caperatic acid, on Wnt signaling in HCT116 and DLD-1 colorectal cancer cell lines
The aim of this study was the evaluation of the effects of depsides and depsidones and a poly-carboxylic fatty acid—caperatic acid, which were derived from different lichen species, on the Wnt signaling in colorectal cancer cell lines
Summary
Lichens, which are symbiotic organisms consisting of fungi and photosynthetic partners (algae and/or cyanobacteria), are a source of a broad group of unique secondary metabolites, many of which possess important biological activities [1, 2]. Investigations using lichen extracts prevail and data describing the action of single compounds are limited. The molecular mechanisms of the observed action of both lichen extracts and single compounds remain largely unknown. Lichen-derived extracts and compounds have been shown to exert antioxidant, antibacterial, antiviral, antipyretic, anti-inflammatory, and cytotoxic activity [2]. Some lichen extracts show selective cytotoxicity towards cancer cells, leaving non-cancerous cells largely unaffected [3]. Lichen compounds may exert anticancer properties due to the ability to induce cell cycle arrest and apoptosis [4,5,6]. This frequently requires the application of high concentrations of the chemicals
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