Griseofulvin as a dual-action agent against glioblastoma: anti-tumor effect and enhancement of 5-ALA photodynamic diagnosis in stem-like cells.

PURPOSE: 5-aminolevulinic acid (5-ALA)-mediated photodynamic diagnosis (PDD), a standard surgical adjunct for glioblastoma (GBM), is limited in its efficacy by heterogeneous protoporphyrin IX (PpIX) accumulation. We investigated the drug repurposing potential of griseofulvin (GF), an antifungal agent, as a dual-action agent that directly inhibits tumor growth through cell cycle arrest and enhances 5-ALA-induced fluorescence by regulating ferrochelatase (FECH). METHODS: The antitumor effects of GF on glioma stem-like cells (NCH644) and other differentiated GBM cell lines were evaluated using cell viability, colony formation, and cell cycle assays. PpIX accumulation and its enhancement by GF were quantified using a time-course analysis. The mechanisms were investigated using western blotting, RT-qPCR, and confocal visualization. An orthotopic GBM mouse model was used to assess in vivo antitumor activity using preliminary ex vivo fluorescence imaging. RESULTS: GF first exerted direct antitumor effects via G2/M arrest, characterized by cyclin D1 downregulation and cyclin B1 transient upregulation. Second, GF attenuated the 5-ALA-induced increase in FECH mRNA levels and enhanced PpIX accumulation. In vivo, oral administration of GF significantly inhibited tumor growth in vivo In a preliminary ex vivo assessment, tumors from GF-treated mice showed a higher tumor-to-normal PpIX fluorescence ratio than those receiving 5-ALA monotherapy, enabling superior tumor visualization. CONCLUSIONS: These preclinical findings identify GF as a candidate dual-action agent for GBM treatment. Whether the fluorescence enhancement translates into improved intraoperative detection, extent of resection, or patient survival remains to be determined through future in vivo and clinical studies.