The impact of evodiamine on human anaplastic thyroid cancer therapy—an <i>in vitro</i> and <i>in vivo</i> study

Thyroid cancer (TC) is the most common endocrine malignancy, with anaplastic thyroid cancer (ATC) being the most aggressive subtype. Evodiamine (EVO), a bioactive compound derived from <i>Evodia rutaecarpa</i>, possesses anti-inflammatory and anti-tumor properties, though its effects on ATC remain underexplored. This study investigated the anticancer potential of EVO using ARO and SW579 ATC cell lines in both <i>in vitro</i> and <i>in vivo</i> models. EVO significantly inhibited cell proliferation, induced G2/M phase arrest, and increased the sub-G1 population, indicating growth inhibition and cell death. Mechanistically, EVO activated the intrinsic caspase-dependent apoptotic pathway and triggered autophagy, as shown by autophagosome accumulation and elevated LC3-II levels. Importantly, blocking autophagy attenuated caspase activation, suggesting that autophagy contributes to EVO-induced apoptosis. Moreover, oral EVO administration markedly suppressed tumor growth in a nude mouse xenograft model without causing liver or kidney toxicity. TUNEL assay further confirmed enhanced tumor cell apoptosis <i>in vivo</i>. These results highlight EVO as a promising therapeutic candidate for ATC by simultaneously activating autophagy and apoptosis pathways.