Abstract
Background/Objectives: Licochalcone A (LA), a bioactive chalcone derived from Glycyrrhiza species, exhibits anticancer activity in several tumor models; however, its effects on endometrial cancer remain poorly understood. This study investigated the antiproliferative, cytotoxic, and antimigratory effects of LA in Ishikawa endometrial cancer cells and characterized associated changes in Akt/mTOR- and LC3-related molecular responses. Methods: Metabolic activity, colony formation, cell cycle distribution, migration, and invasion were evaluated following LA treatment. Ki-67 and LC3-II immunoreactivity, PI3K, Akt, mTOR, and MAP1LC3B transcript levels, and Akt phosphorylation were also assessed. Results: LA reduced metabolic activity and clonogenic capacity, decreased Ki-67 expression after prolonged exposure, increased apoptosis, and induced S-phase accumulation at higher concentrations. LA markedly reduced cell migration after 48 h, whereas no statistically significant change in invasion was detected. RT-qPCR revealed concentration- and time-dependent changes in PI3K, Akt1, mTOR, and MAP1LC3B transcript levels, with mTOR significantly reduced at all tested concentrations after 48 h. Akt phosphorylation was markedly reduced across all tested concentrations after 48 h, while MAP1LC3B transcript levels and LC3-II immunoreactivity showed concentration- and time-dependent changes. Conclusions: These findings demonstrate antiproliferative, cytotoxic, and antimigratory effects of LA in Ishikawa endometrial cancer cells and identify associated changes in Akt/mTOR- and LC3-related molecular responses.