Air Plasma-Activated Medium Evokes a Death-Associated Perinuclear Mitochondrial Clustering

Area of Science:

• Biomedical Engineering
• Cancer Research
• Cell Biology

Background:

• Intractable cancers like osteosarcoma (OS) and oral cancer (OC) exhibit high refractoriness, recurrence, and metastasis, leading to poor prognoses.
• Current tumor-targeted therapies often face resistance, necessitating exploration of alternative cell death modalities beyond apoptosis.
• Tumor-specific activation of novel cell death pathways presents a promising strategy for effective and safe cancer treatment.

Purpose of the Study:

• To investigate the anti-cancer effects of cold atmospheric air plasma-activated medium (APAM) on osteosarcoma and oral cancer.
• To identify and characterize the unique cell death mechanism induced by APAM in tumor cells.
• To explore the potential of APAM-induced cell death as a tumor-specific therapeutic strategy.

Main Methods:

• Treatment of OS and OC cells with APAM.
• Microscopic observation of cellular and mitochondrial morphology, including mitochondrial clustering and nuclear damage.
• Measurement of reactive oxygen species (ROS) and lipid peroxidation levels.
• Assessment of cell death (apoptotic and non-apoptotic).
• Evaluation of the effects of antioxidants (NAC, Ferrostatin-1) and microtubule inhibitor (Nocodazole).
• Comparison of APAM effects on cancer cells versus normal fibroblasts.

Main Results:

• APAM effectively killed OS and OC cells through a unique process termed monopolar perinuclear mitochondrial clustering (MPMC).
• MPMC involved mitochondrial fragmentation, nuclear damage, increased mitochondrial ROS (mROS), and mitochondrial lipid peroxidation (mLPO).
• Antioxidants (NAC, Ferrostatin-1) and Nocodazole inhibited MPMC and associated cell death, indicating roles for oxidative stress and microtubule dynamics.
• APAM exhibited tumor-specific cytotoxicity, inducing minimal effects on fibroblasts.

Conclusions:

• MPMC is a novel, tumor-specific cell death modality induced by APAM in OS and OC.
• This process is driven by mitochondrial oxidative stress and microtubule-dependent mitochondrial motility.
• Targeting MPMC represents a promising strategy for developing novel, effective cancer therapies with reduced side effects.