Prodigiosin inhibits proliferation and metastasis in head and neck squamous cell carcinoma: insights from phenotypic validation and network pharmacology

作者：Xin-hui Mao, Xin-hui Mao, Xinhui Mao, Xinhui Mao, Huiying Huang, Limin Zhao, Teng Zhou, Jinlu Han, Xiaohui Yuan, Feiran Li, Zhenwei Wang, Simin Liang, Chi‐Yao Hsueh, Hui‐Ching Lau, Ming Zhang · 发表于：Bioorganic Chemistry · 年份：2026 · DOI：10.1016/j.bioorg.2026.109841 · 研究领域：Microbial Metabolism and Applications、Ferroptosis and cancer prognosis、Microbial Metabolic Engineering and Bioproduction

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) exhibits significant heterogeneity and poor survival rates in advanced stages, necessitating novel therapeutic strategies. Prodigiosin, a natural bacterial metabolite with demonstrated anticancer properties in other malignancies, has not been thoroughly investigated in HNSCC. This study aimed to investigate the antitumor effects of prodigiosin and elucidate its underlying mechanisms in HNSCC. METHODS: An integrated approach combining network pharmacology prediction with experimental validation was employed. In vitro assays (CCK-8, EdU, colony formation, tumorsphere, transwell migration and invasion) assessed prodigiosin's effects on carcinogenesis across HNSCC cell lines. A subcutaneous xenograft mouse model evaluated antitumor efficacy and lymph node metastasis in vivo. Potential targets and pathways identified by network pharmacology were subsequently validated through molecular docking followed by 100-ns molecular dynamics simulations. Functional experiments were performed to the effect of prodigiosin on HNSCC targets and pathway. RESULTS: Prodigiosin potently inhibited HNSCC proliferation in vitro and significantly suppressed tumor growth in vivo. In addition, it attenuated cancer stemness, migration, and invasion, and significantly reduced the lymph node metastatic burden in mice. Network analysis identified 159 shared targets, with EGFR, BCL2, ERBB2, PPARG, and PTGS2 identified as core hubs. Enrichment analysis h...