Work

Reactive Oxygen Species–Driven Mitochondrial Apoptotic Signaling and ER Stress Responses in HNSCC Cells Treated with Cold Atmospheric Plasma

Year: 2026

Type: preprint

Abstract: Objective: Head and neck squamous cell carcinoma (HNSCC) remains a challenging cancer with poor survival and significant treatment-related morbidity. Cold atmospheric plasma (CAP) has potential anticancer effects; however,its specific molecular mechanisms in HNSCC remain incompletely understood. This study examined the antitumor actions of CAP on HNSCC together with associated ROS-mediated mitochondrial pathways. Methods: Two HNSCC cell lines (FaDu and TU212) were treated with CAP for varying durations (0–240 s). Cell viability and migration were evaluated using CCK-8 and wound-healing assays, respectively, while apoptosis was examined using flow cytometry. Intracellular ROS levels were quantified. The activation of mitochondrial apoptotic pathway was evaluated by Western blotting for key markers (Bax,Blc-2 and cleaved caspase-3) and transmission electron microscopy. Furthermore, antitumor effects were verified using a FaDu xenograft mouse model, with tumor growth,proliferation (Ki-67),and apoptosis(C-Caspase-3) analyzed via immunofluorescence. Results: CAP administration led to marked time-dependent reductions in HNSCC cell viability and migration.Mechanistically, CAP persistently elevates intracellular ROS, triggering mitochondrial pathway-mediated apoptosis and ER stress, and marked ultrastructural changes including ER vacuolization and nuclear fragmentation. In mice, CAP administration markedly suppressed tumor growth without causing systemic toxicity or skin damage, correlating with reduced proliferation and enhanced apoptosis within the tumor microenvironment. Conclusion: CAP exerts potent antitumor effects against HNSCC by inducing a self-amplifying oxidative stress response that activates endogenous apoptosis and endoplasmic reticulum stress. These results indicate the potential of CAP in treating HNSCC and provide a mechanistic rationale for its future clinical translation.

Source: Research Square

DOI: 10.21203/rs.3.rs-11434517/v1

Authors: yan Zang, Zhimin Ding, Chengbiao Ding, zongshi Gao, dongyu SI, zhan Gao, zhengwei Wu, huabing Zhang, chaobing Gao

Institutions: First Affiliated Hospital of Anhui Medical University, Second Affiliated Hospital of Anhui Medical University, University of Science and Technology of China, Anhui Medical University

Language: English

Topic: Atmospheric-Pressure Plasma Applications

Subfield: Atomic and Molecular Physics, and Optics

Field: Physics and Astronomy

Domain: Physical Sciences

Open Access status: green

OpenAlex ID: W7225778114

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