Lichen metabolites differentially modulate the JAK/STAT signaling pathway in MCF-7 cells

Lichen-derived metabolites have demonstrated anticancer potential, but their effects on JAK/STAT signaling and associated immune-related gene expression in breast cancer remain unclear. This study investigated whether evernic acid (EA), diffractaic acid (DA), and vulpinic acid (VA) modulate JAK/STAT signaling and related inflammatory, immune-associated, and angiogenic responses in MCF-7 cells.

Cells were treated with each compound at its previously determined 52 h IC₅₀ concentration. The mRNA expression of JAK1, JAK2, STAT3, IL6, TNF, IFNG, and VEGFA was analyzed by quantitative real-time PCR (qRT-PCR), and phosphorylated JAK1, JAK2, and STAT3 levels were assessed by Western blotting. EA and VA treatment was associated with reduced JAK1, JAK2, and STAT3 mRNA expression and lower levels of phosphorylated JAK1, JAK2, and STAT3, accompanied by decreased IL6 expression. In contrast, DA increased the expression of JAK/STAT-associated genes and increased p-JAK1 and p-STAT3 levels, whereas p-JAK2 levels were not significantly altered. The compounds also differentially affected TNF, IFNG, and VEGFA expression. Notably, EA increased IFNG expression without significantly altering VEGFA expression.

EA and VA were associated with reduced JAK/STAT3-related signaling markers, whereas DA produced a distinct response pattern. These findings demonstrate differential molecular responses to the three lichen metabolites under the tested conditions. Further studies are needed to establish the specificity of these responses and determine their biological significance.