Cell Death Mechanism by Dual Treatments of Nanosecond Electric Pulses and Cold Atmospheric Plasma
Document Type
Abstract
Publication Date
11-7-2024
DOI
10.25776/661d-nc93
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths worldwide, marked by its aggressive behavior and therapeutic resistance. Despite advancements in cancer research, effective treatment options remain limited, highlighting the urgent need for innovative approaches. Our previous reports showed a synergistic effect of combined nanopulse (NP) and cold atmospheric plasma (CP) treatments enhancing cytotoxicity in pancreatic cancer cells. This study aims to investigate the mechanisms driving this synergy, focusing on how NP and CP jointly induce cell death in pancreatic cancer cells.
Reactive oxygen species (ROS) levels and mitochondrial membrane potential (Δψm) were measured by flow cytometry to quantify oxidative stress and assess mitochondrial function, respectively. Cell death pathways activated by NP and CP treatments were analyzed by Western Blot and enzyme activity assays. Additionally, proteomic analysis using mass spectrometry (MS) was carried out to identify potential molecular events associated with cytotoxicity. Flow cytometry analysis showed a minimal increase in reactive oxygen species (ROS) levels and a slight drop in mitochondrial membrane potential (Δψm) with individual NP and CP treatments. In contrast, the combined NP and CP treatments led to markedly increase in ROS levels and a significant reduction in (Δψm) compared to single treatments. These findings imply that oxidative stress and disrupted mitochondrial function may play key roles in the observed cell death. Specifically, CP treatment induces apoptotic cell death, marked by the activation of Caspase 3/7, while NP treatment triggers non-apoptotic, non-pyroptotic cell death pathways, with no activation of Caspase 3/7 or Caspase 1. Together, our results reveal that NP and CP activate distinct cell death mechanisms that collectively contribute to the enhanced cytotoxicity observed in combination treatments.
Repository Citation
Minhas, Zobia; Oshin, Edwin A.; Yang, Lifang; Jiang, Chunqi; and Guo, Siqi, "Cell Death Mechanism by Dual Treatments of Nanosecond Electric Pulses and Cold Atmospheric Plasma" (2024). 2024 Frank Reidy Research Center for Bioelectrics Retreat. 9.
https://digitalcommons.odu.edu/bioelectrics-2024retreat/9
