Abstract
Cervical cancer remains a leading cause of cancer-related mortality, emphasizing the need for safer, more selective therapies. Yttrium oxide nanoparticles (Y(2)O(3)-NPs) have unique physicochemical properties, but their anticancer potential in cervical carcinoma remains underexplored. This study therefore estimated the cytotoxic effects of Y(2)O(3)-NPs in HeLa cervical cancer cells and normal HFB4 melanocytes, with mechanistic analyses focused on HeLa cells. Cells were exposed to Y₂O₃-NPs various concentrations and viability was assessed via MTT assay. Mechanistic endpoints; including total ROS generation, mitochondrial membrane potential, DNA damage, apoptotic morphology, and expression of apoptosis- and mitochondria-related genes, were analyzed using fluorescence assays, alkaline Comet assay, nuclear staining, and quantitative RT-PCR. Y(2)O(3)-NPs reduced HeLa cell viability in a concentration-dependent manner with markedly low IC50 value of 52.22 µg/mL (0.231 mM), whereas HFB4 cells were less affected and exhibited markedly greater IC50 value of 264.10 µg/mL (1.169 mM); high selectivity index of 5.06 demonstrating preferential cytotoxicity toward Hela cancer cells. Exposure to the IC50 concentration induced marked ROS overproduction, dramatic mitochondrial depolarization, severe DNA damage, and observable apoptotic nuclear changes in cancerous HeLa cells, accompanied by upregulation of apoptotic p53, anti-apoptotic Bcl-2, and mitochondrial ND3 gene expression. Conclusion: These findings Y(2)O(3)-NPs exert strong and selective cytotoxic effects against HeLa cervical cancer cells while causing minimal toxicity to normal HFB4 melanocytes. This preferential cytotoxicity appears to be mediated by Y(2)O(3)-NPs–induced oxidative stress, genomic DNA damage, mitochondrial depolarization, and activation of mitochondrial-related apoptotic pathways. Although these results highlight the potential anticancer activity of Y(2)O(3)-NPs, further in vivo studies and detailed mechanistic investigations are needed to confirm their therapeutic efficacy and safety.