An Evaluation of the Cytotoxicity and Safety Profile of Usnic Acid for a Broad Panel of Human Cancers and Normal Cells with Respect to Its Enantiospecificity

Chirality plays a key role in the effectiveness and toxicity of bioactive compounds. Usnic acid (UA), a lichen metabolite, exists as two enantiomers. Despite numerous studies on its biological properties, enantioselective aspects remain poorly recognized. This study assessed the cytotoxicity of UA enantiomers against colon, prostate, thyroid, brain, and breast cancer cell lines, as well as non-cancerous cells. Cell viability was determined by the MTT assay after 24, 48, and 72 h. Colon cancer HCT116 cells were the most sensitive (IC₅₀ ~10 µg/mL, 72 h), with no enantiomeric dominance. In prostate cancer PC3 cells, (+)-UA was more effective. Moderate cytotoxic effect was noted for thyroid cancer cells; however, this was evaluated for the first time. MDA-MB-231 breast cancer cells were strongly affected (IC₅₀ 15.8 and 20.2 µg/mL for (+)- and (-)-UA, 72 h), as compared to MCF7 cells. Brain cancer cells were the least affected, as so were normal astrocytes. UA had no effect on normal colon epithelial cells but showed moderate toxicity in prostate, thyroid, and breast cells. To conclude, the overall cytotoxicity of (+)-UA was stronger than its (-)-enantiomer, while the latter compound was more toxic to normal cells. These findings highlight the advantage of (+)-UA, especially in chemopreventive strategies.