Arsenic-Based Homeopathic Preparations Induce Metabolic Disruption and Reactive Oxygen Species-Mediated Cell Death in Glioblastoma Multiforme

BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with a poor median survival rate. There is an urgent need for effective and affordable anti-cancer agents for GBM treatment. In this context, arsenic-based homeopathic preparations may serve as promising therapeutic candidates. OBJECTIVES: This study aimed to evaluate the efficacy of Arsenicum iodatum and Arsenicum album-induced cytotoxicity in GBM cells and to investigate the underlying mechanisms of action in the U-87-MG and LN-229 cell lines. RESULTS: Treatment with varying concentrations of Arsenicum iodatum and Arsenicum album resulted in dose- and time-dependent inhibition of GBM cells growth in U87-MG and LN-229. These preparations induced distinct morphological changes and cell death in both GBM cell lines. Gas chromatography-mass spectrometry (GC-MS)-based metabolomics revealed significant alterations in the key metabolic pathways. A total of 107 metabolites were quantified. Univariate analysis identified 73 and 30 significantly altered metabolites in Arsenicum album-treated U-87-MG and LN-229 cells, respectively. Meanwhile, U-87 showed 69 and LN-229 showed 50 significantly affected metabolites in the Arsenicum iodatum-treated groups. In GBM cells treated with Arsenicum album and Arsenicum iodatum, glycine and serine, which are involved in redox balance, were altered, while branched-chain amino acids (valine, leucine, isoleucine)- essential for protein synthesis and mTOR signaling- were downregulated. Changes were also observed in nucleotide sugar, purine, and nicotinate/nicotinamide metabolism. The findings suggest that both agents cause strong metabolic disruptions, potentially contributing to their anti-cancer effects. Biochemical assays confirmed increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential following treatment with these arsenic based homeopathic preparation. CONCLUSION: Arsenicum iodatum and Arsenicum album exhibit growth-inhibitory effects on GBM cells, likely through metabolic disruption and ROS-mediated cell death. Further studies are warranted to elucidate the precise mechanisms of cell death and to evaluate their efficacy and safety in vivo.