Evaluation of the anti-tumor efficacy of prodigiosin in papillary thyroid cancer cell and animal models.

OBJECTIVE: To investigate the anti-tumor efficacy and underlying molecular mechanisms of prodigiosin (PG) in papillary thyroid cancer (PTC). METHODS: The anti-cancer effects of PG were systematically evaluated in vitro using PTC cell lines and in vivo via xenograft mouse models. Cell viability and dose-response relationships were determined by CCK-8 assays. Anti-proliferative activity was assessed through colony formation and EdU incorporation assays. The impact on metastatic potential was examined by scratch wound healing and Matrigel-based transwell migration and invasion assays. Cell cycle distribution was analyzed using flow cytometry. RESULTS: In vitro, PG at 500 nM inhibited the growth of BCPAP and TPC-1 cells by 93.5 % and 89.2 %, respectively, as determined by colony formation assays. Migration and invasion of BCPAP cells were reduced by 90.7 % and 93.4 %, measured via scratch wound healing and transwell assays. PG treatment modulated epithelial-mesenchymal transition (EMT) markers both in vitro and in vivo, characterized by downregulating mesenchymal proteins and upregulating epithelial proteins, accompanied by changes in Wnt/β-catenin pathway-related proteins, indicating suppression of EMT. Flow cytometry revealed that PG induced G0/G1 cell cycle arrest in both BCPAP and TPC-1 cells. Furthermore, PG upregulated the sodium-iodide symporter (NIS), enhancing radioiodine uptake. Moreover, the treatment of PG significantly inhibited tumor growth without notable toxicity in vivo. CONCLUSION: PG exerts potent anti-tumor activity against PTC by simultaneously inhibiting proliferation, migration, and invasion, inducing cell cycle arrest, and enhancing radioiodine uptake, potentially through modulation of the Wnt/β-catenin signaling pathway. Our findings position PG as a highly promising, potentially transformative therapeutic candidate for PTC, offering a strategic approach to overcome conventional therapy resistance and improve clinical outcomes.