Journal Article

Calcium hydroxide nanoparticles induce apoptotic cell death in human pancreatic cancer cells through over ROS-driven genomic instability and mitochondrial dysfunction

Diab, Ayman, Elberry, Yusuf, Michael, Maivel, Eltayeb, Nourhan, Safwat, Gehan, Ismail, Maryam, Magdy, Hagar, Mohamed, Hanan R. H.

2025

Overview

The aggressive nature of pancreatic cancer, coupled with the limitations of current treatment options, underscores the urgent need for more effective and targeted therapies. Nanoparticle-based approaches offer promising alternatives, with calcium hydroxide nanoparticles (Ca(OH) 2 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) 2 NPs on the viability of normal oral epithelial cells (OECs) and pancreatic cancer PANC-1 cells, moreover, the impact of Ca(OH) 2 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) 2 NPs on PANC-1 cells following exposure to five different concentrations (0.01, 1, 10, 100, and 1000 µg/ml) for 72 h, with an IC50 value of 152.40 µg/ml. In contrast, minimal cytotoxicity was observed in normal OECs, which had an IC50 value of 481.66 µg /ml. The calculated selectivity index of 3.16 further confirmed the preferential cytotoxicity of Ca(OH) 2 NPs towards PANC-1 cells. Moreover, exposure of PANC-1 cells to the IC50 concentration of Ca(OH) 2 NPs (152.40 µg/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) 2 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) 2 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/154 / 631/45 / 631/67 / 631/80 / Alkalinity / Apoptosis / Apoptosis - drug effects / Apoptosis - genetics / Bcl-2 protein / Biocompatibility / Ca(OH)2 NPs / Calcium hydroxide / Calcium Hydroxide - pharmacology / Calcium Hydroxide - therapeutic use / Cancer therapies / Cell death / Cell Line, Tumor / Chemotherapy / Cytotoxicity / Deoxyribonucleic acid / DNA / DNA damage / DNA stability / Drug Screening Assays, Antitumor / Epithelial cells / Gene expression / Gene Expression Regulation, Neoplastic - drug effects / Genomic instability / Genomic Instability - drug effects / Genomics / Humanities and Social Sciences / Humans / Inhibitory Concentration 50 / Mitochondria - drug effects / Mitochondria - pathology / Mitochondrial apoptosis / Mitochondrial DNA / Mitochondrial Membranes - drug effects / Mitochondrial Membranes - pathology / Molecular modelling / multidisciplinary / Nanoparticles / Nanoparticles - therapeutic use / Nanotechnology / p53 Protein / PANC-1 cells / Pancreatic cancer / Pancreatic Neoplasms - drug therapy / Pancreatic Neoplasms - genetics / Pancreatic Neoplasms - pathology / Particle size / Reactive Oxygen Species / ROS generation / Science / Science (multidisciplinary) / Sulforhodamine / Toxicity / Transmission electron microscopy / Tumor microenvironment