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Research Article

Silver nanoparticles induce apoptosis via NOX4-derived mitochondrial reactive oxygen species and endoplasmic reticulum stress in colorectal cancer cells

    Juan-Hua Quan‡

    Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524-001, People's Republic of China

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Fei Fei Gao‡

    Brain Korea 21 Four Project for Medical Science, Chungnam National University, Daejeon 35015, Korea

    Departments of Medical Science and Department of Infection Biology, Chungnam National University College of Medicine, Daejeon 35015, Korea

    ‡Authors contributed equally

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    ,
    Jia-Qi Chu‡

    Stem Cell Research & Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524-001, People's Republic of China

    ‡Authors contributed equally

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    ,
    Guang-Ho Cha

    Departments of Medical Science and Department of Infection Biology, Chungnam National University College of Medicine, Daejeon 35015, Korea

    ,
    Jae-Min Yuk

    Brain Korea 21 Four Project for Medical Science, Chungnam National University, Daejeon 35015, Korea

    Departments of Medical Science and Department of Infection Biology, Chungnam National University College of Medicine, Daejeon 35015, Korea

    ,
    Weiyun Wu

    *Author for correspondence: Tel.: +82 42 580 8273;

    E-mail Address: yhalee@cnu.ac.kr

    Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524-001, People's Republic of China

    &
    Young-Ha Lee

    *Author for correspondence: Tel.: +82 42 580 8273;

    E-mail Address: yhalee@cnu.ac.kr

    Brain Korea 21 Four Project for Medical Science, Chungnam National University, Daejeon 35015, Korea

    Departments of Medical Science and Department of Infection Biology, Chungnam National University College of Medicine, Daejeon 35015, Korea

    Published Online:https://doi.org/10.2217/nnm-2021-0098

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

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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