Silver Nanoparticles Induce Apoptosis Via <i>Nox4</i> -Derived Mitochondrial Reactive Oxygen Species and Endoplasmic Reticulum Stress in Colorectal Cancer Cells

Abstract

<b>Aim:</b> To investigate the anticancer mechanisms of silver nanoparticles (AgNPs) in colorectal cancer. <b>Methods:</b> Anticancer effects of AgNPs were determined in colorectal cancer HCT116 cells and xenograft mice using cellular and molecular methods. <b>Results:</b> AgNPs induced mitochondrial reactive oxygen species production, mitochondrial dysfunction and endoplasmic reticulum (ER) stress responses through <i>NOX4</i> and led to HCT116 cell apoptosis. Pretreatment with DPI or 4-PBA significantly inhibited mitochondrial reactive oxygen species production, apoptosis, ER stress response, <i>NOX4</i> expression and mitochondrial dysfunction in AgNP-treated HCT116 cells. AgNPs also significantly suppressed HCT116 cell-based xenograft tumor growth in nude mice by inducing apoptosis and ER stress responses. <b>Conclusion:</b> AgNPs exert anticancer effects against colorectal cancer via ROS- and ER stress-related mitochondrial apoptosis pathways.