Evaluating the impact of Xanthoparmelia conspersa extracts on signaling in HeLa cells and exploring their diverse biological activities.

Xanthoparmelia conspersa is rich in specific secondary metabolites but an unexplored lichen species. This work determined the chemical composition and biological activities (anti-microbial, anti-protozoal, and cytotoxic) of its methanolic and hexane extracts. Additionally, we evaluated the potential of these extracts in modulating cancer signaling pathways in HeLa cells. The phytochemical analysis revealed that usnic acid was the predominant constituent in the hexane extract, while stictic acid was in the methanolic one. Among tested cell lines (VERO, FaDu, SCC-25, HeLa), cytotoxic selectivity was detected for X. conspersa hexane extract against the FaDu (SI 7.36) and HeLa (SI 2.19) cells. A noticeably better anti-microbial potential was found for hexane extract, however, the overall anti-microbial activity was relatively weak (28, 21, and 20% inhibition of Candida glabrata, Cryptococcus neoformans, and Escherichia coli, respectively). On the contrary, the anti-parasitic action of hexane extract was significant, with an IC value of 2.64 µg/mL against Leishmania donovani - amastigote and 7.18 µg/mL against Trypanosoma brucei. The detailed evaluation of the cancer-related signaling pathways in HeLa cells, done by two distinct methodologies (luciferase reporter tests), revealed that especially the hexane extract and usnic acid exhibited selective inhibition of Stat3, Smad, NF-κB, cMYC, and Notch pathways.