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.