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Nanoparticle-based approaches offer promising alternatives, with calcium hydroxide nanoparticles (Ca(OH)\n                    <jats:sub>2<\/jats:sub>\n                    NPs) emerging as a potential candidate due to their biocompatibility, high alkalinity, and ability to modify the tumor microenvironment. However, their therapeutic potential against pancreatic cancer remains largely unexplored. This study thus estimated the effects of Ca(OH)\n                    <jats:sub>2<\/jats:sub>\n                    NPs on the viability of normal oral epithelial cells (OECs) and pancreatic cancer PANC-1 cells, moreover, the impact of Ca(OH)\n                    <jats:sub>2<\/jats:sub>\n                    NPs on genomic DNA and mitochondrial membrane integrity, reactive oxygen species (ROS) generation, and apoptosis induction in PANC-1 cells was assessed. Sulforhodamine B cytotoxicity assay demonstrated a strong, targeted concentration-dependent cytotoxic effect of Ca(OH)\n                    <jats:sub>2<\/jats:sub>\n                    NPs on PANC-1 cells following exposure to five different concentrations (0.01, 1, 10, 100, and 1000\u00a0\u00b5g\/ml) for 72\u00a0h, with an IC50 value of 152.40\u00a0\u00b5g\/ml. In contrast, minimal cytotoxicity was observed in normal OECs, which had an IC50 value of 481.66\u00a0\u00b5g \/ml. The calculated selectivity index of 3.16 further confirmed the preferential cytotoxicity of Ca(OH)\n                    <jats:sub>2<\/jats:sub>\n                    NPs towards PANC-1 cells. Moreover, exposure of PANC-1 cells to the IC50 concentration of Ca(OH)\n                    <jats:sub>2<\/jats:sub>\n                    NPs (152.40\u00a0\u00b5g\/ml) led to excessive ROS generation, marked genomic instability, and loss of mitochondrial membrane integrity. These effects were accompanied by dysregulation of key apoptotic genes, including upregulation of p53 and mitochondrial ND3, along with downregulation of the anti-apoptotic Bcl-2 gene, ultimately inducing mitochondrial apoptosis in PANC-1 cells. Ca(OH)\n                    <jats:sub>2<\/jats:sub>\n                    NPs exhibit potent, selective cytotoxicity against PANC-1 cells while exerting minimal toxicity on normal OECs. Their mechanism of action appears to involve excessive ROS generation, leading to severe genomic DNA and mitochondrial damage, ultimately triggering apoptosis in pancreatic cancer cells. These findings highlight the potential of Ca(OH)\n                    <jats:sub>2<\/jats:sub>\n                    NPs as a novel therapeutic agent for pancreatic cancer. However, further in vitro and in vivo studies are warranted to fully explore their clinical applicability and underlying molecular mechanisms in pancreatic cancer treatment.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-26135-5","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T09:57:46Z","timestamp":1763459866000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Calcium hydroxide nanoparticles induce apoptotic cell death in human pancreatic cancer cells through over ROS-driven genomic instability and mitochondrial dysfunction"],"prefix":"10.1038","volume":"15","author":[{"given":"Hanan R. 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