Baicalin induces apoptosis in thyroid Cancer C643 cells via BCL2 downregulation and PI3K-AKT pathway modulation

Baicalin, a flavonoid derived from Scutellaria baicalensis, exhibits broad antitumor activity. However, its effects on anaplastic thyroid cancer (ATC) C643 cells remain unclear. This study investigated the inhibitory capacity and underlying mechanisms of baicalin against C643 cells using both in vitro and in vivo models. In vitro, including CCK-8 viability assay, scratch-wound healing assay, transwell migration, Annexin V-FITC/PI apoptosis, cell-cycle and JC-1 mitochondrial membrane potential assays demonstrated that baicalin reduced cell viability and migration in a concentration-and time-dependent manner, induced G2-phase arrest and decreased mitochondrial membrane potential. Integrated transcriptome sequencing identified BCL2 and the PI3K-AKT pathway as key targets. qPCR and western blot confirmed that baicalin down-regulated BCL2 in a dose-dependent manner, selectively activated the PI3K-AKT cascade, promoted TP53 recruitment to the BAX/BIM promoters and up-regulated their transcription, accompanied by increased p-PI3K and p-AKT levels. In vivo, daily intraperitoneal administration of 50 mg/kg baicalin for 21 days led to a 55.6 % reduction in C643 xenograft volume. Immunohistochemistry revealed decreased BCL2 and Ki-67 expression in tumor tissues, indicating impaired anti-apoptotic activity and proliferative capacity. Importantly, histopathological examination of major organs (heart, liver, spleen, lung and kidney) showed no treatment-related toxicity, confirming the safety of baicalin. These findings demonstrate that baicalin is a safe, multi-target therapeutic candidate with a well-defined mechanism, offering a novel and effective targeted option for aggressive anaplastic thyroid cancer. • First RNA-seq to validate baicalin targets and pathways in thyroid cancer. • Baicalin suppresses C643 cell growth by blocking the PI3K-AKT signaling pathway. • Baicalin triggers apoptosis and cell cycle arrest, enhancing antitumor efficacy.