Cancers, Vol. 17, Pages 3432: Cold Atmospheric Plasma Selectively Targets Neuroblastoma: Mechanistic Insights and In Vivo Validation

Cancers doi: 10.3390/cancers17213432

Authors:
Ligi Milesh
Bindu Nair
Ha M. Nguyen
Taylor Aiken
J. Leon Shohet
Hau D. Le

Background: Neuroblastoma (NB) presents significant challenges in pediatric oncology, particularly in high-risk cases where local recurrence occurs in ~35% of patients. Cold Atmospheric Plasma (CAP) has emerged as a promising treatment due to its selective cytotoxicity toward cancer cells while sparing normal cells. Methods: This study assessed CAP efficacy using in vitro NB cell lines (SK-N-AS and LAN-5) and in vivo xenograft murine models. In vitro, CAP was applied via a helium jet, and cellular responses were evaluated for viability, reactive oxygen species (ROS), lipid peroxidation, DNA damage, and cell cycle, while apoptosis was measured by Annexin V/PI flow cytometry. In vivo, CAP was applied to unresected tumors and residual tumors after incomplete resection. Tumor regrowth was monitored, and histological analysis was performed. Results: CAP reduced NB cell viability in a dose- and time-dependent manner by increasing intracellular ROS and lipid peroxidation. CAP-treated NB cells showed a 50% rise in oxidative DNA damage, a two-fold increase in apoptosis, and alterations in cell-cycle progression, while normal fibroblasts showed modest effects. CAP predominantly induced apoptosis, though secondary necrosis appeared with prolonged exposures, consistent with caspase-3 and PARP pathways. In xenografts, CAP reduced tumor diameter by 60% and increased caspase-3-positive cells, with minimal effects on normal tissue. Conclusions: CAP demonstrates strong therapeutic potential as a targeted, non-invasive NB treatment, particularly for residual tumors near vascular structures with consistent exposure times (60–300 s).

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Ligi Milesh www.mdpi.com