Anticancer activity of lichen-derived compounds against triple-negative breast cancer: integrated in vitro evaluation, network pharmacology, molecular docking, and KEGG pathway analysis.

Authors

Sachin V Mapari, Subhash B Gaikwad, Ruchira R Sutar, Roshni Khare, Ravindra M Patil, Bhaskar C Behera

Published in

Naunyn-Schmiedeberg's archives of pharmacology. Aug 15, 2026. Epub Aug 15, 2026.

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype that lacks ER, PR, and HER2, which results in limited treatment options and poor outcomes. Lichens are symbiotic organisms known for producing unique secondary metabolites and have a history of use in folk medicine. This study investigated the effects of lichen-derived compounds on MDA-MB-231 cells using integrated in vitro and in silico approaches to explore their anticancer potential and potential molecular targets. Six lichen compounds were isolated, characterized, and tested for antioxidant properties using DPPH and ABTS assays. In vitro cytotoxicity was evaluated on MDA-MB-231 using the MTT and FACS assays. ADMET was evaluated using SwissADME and ADMETLab3; GeneCards was used to retrieve the TNBC-associated genes. The STRING database is used to construct the protein-protein interaction network. Molecular docking analysis was done using CB Dock 2. Structural fluctuation was evaluated in CABS-flex 3.0 web server, and an open-source web-based platform, ShinyGO, was used for functional enrichment analysis. Out of six studied lichens, the extract of Everniastrum cirrhatum showed comparatively stronger antioxidant activity in terms of DPPH and ABTS radical scavenging potential. A decrease of up to 80% in cell viability at 320 µg/mL was observed when treated with Everniastrum cirrhatum, Heterodermia boryi, and Usnea longissima extracts. Six lichen compounds were isolated and characterized. ADMET analysis of isolated compounds suggests that they have acceptable drug-like characteristics with minimal major organ toxicity. The analysis of cytotoxicity using MTT and flow cytometry demonstrated a clear dose-dependent reduction in cell viability by atranorin (ATR), barbatic acid (BAR), and usnic acid (USN). Top 14 TNBC-associated hub genes were identified, and molecular docking analysis suggested that ATR and BAR have favorable binding affinities toward AKT1 and mTOR. RMSF analysis predicted reduced structural fluctuations in selected regions of AKT1 and mTOR following ligand binding, suggesting potential stabilization while preserving overall protein dynamics. KEGG pathway enrichment indicated that these hub genes are enriched in cancer-related pathways, including endometrial cancer and central carbon metabolism in cancer, and are associated with the PI3K/AKT/mTOR and RAS/MAPK signaling pathways. Lichen-derived compounds atranorin, barbatic acid, and usnic acid demonstrated anticancer activity in vitro, while integrated computational analyses suggested potential multitarget interactions that warrant further experimental validation.

PMID:
42603184
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

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