Anti-Invasive and Apoptotic Effect of Eupatilin on YD-10B Human Oral Squamous Carcinoma Cells

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy characterized by high invasiveness and poor prognosis. This study investigated the anticancer mechanisms of eupatilin, a pharmacologically active flavonoid derived from Artemisia species, in human OSCC YD-10B cells. Eupatilin significantly reduced cell viability in a dose-dependent manner, with an IC₅₀ of approximately 50 μM. Flow cytometric analysis revealed G0/G1 phase arrest accompanied by downregulation of Cyclin D1 and CDK2, and upregulation of p21. Annexin V/Propidium Iodide staining and Western blotting confirmed apoptosis induction through activation of Bax, cleaved caspase-3/9, and poly ADP-ribose polymerase (PARP) cleavage, alongside suppression of Bcl-2. Furthermore, eupatilin markedly decreased both the mRNA expression and enzymatic activities of matrix metalloproteinases (MMP)-2 and MMP-9, indicating its potential to inhibit cancer cell invasion. Collectively, these findings demonstrate that eupatilin exerts potent antiproliferative and anti-invasive effects on OSCC cells via cell-cycle modulation and mitochondrial-mediated apoptosis. This study provides the first evidence of eupatilin's therapeutic potential against OSCC, suggesting its promise as a natural compound for the development of safer and more effective treatments for oral cancer.