Beauvericin Induces Mitochondrial Apoptosis and Attenuates EMT-Associated Phenotypes and Angiogenic Signaling in Colorectal Cancer Cells .

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, largely due to metastasis and therapeutic resistance. Beauvericin, a cyclohexadepsipeptide mycotoxin produced by and species, has demonstrated anticancer activity in multiple malignancies; however, its mechanistic effects in CRC have not been fully defined. In this study, we investigated the cellular and molecular effects of beauvericin in HCT116 and SW480 CRC cells using models. Beauvericin reduced cell viability and clonogenic growth, induced G0/G1 cell-cycle arrest, and activated mitochondria-dependent apoptosis through modulation of Bcl-2 family proteins and caspase activation. At sub-cytotoxic concentrations, beauvericin significantly suppressed migratory and invasive phenotypes and attenuated epithelial-mesenchymal transition (EMT)-associated features, accompanied by reduced activation of integrin α6/FAK/Src/ERK1/2 signaling without altering total protein expression. Conditioned medium from beauvericin-treated CRC cells markedly inhibited endothelial proliferation, invasion, and tube formation, coinciding with reduced VEGF secretion. Network-based target prediction and immunoblot validation further demonstrated that beauvericin treatment was associated with decreased phosphorylation of JAK2, STAT1, and STAT3. Collectively, these findings indicate that beauvericin modulates multiple malignant phenotypes of CRC cells by inducing mitochondrial apoptosis and attenuating EMT-associated signaling, VEGF-dependent endothelial activation, and JAK/STAT pathway activity. These results provide mechanistic insight into the anti-tumor potential of beauvericin and support further preclinical evaluation.