Non-Thermal Atmospheric Pressure Plasma Preferentially Induces Apoptosis in p53-Mutated Cancer Cells by Activating ROS Stress-Response Pathways

Abstract

Non-thermal atmospheric pressure plasma (NTAPP) is an ionized gas at room temperature and has potential as a new apoptosis-promoting cancer therapy that acts by generating reactive oxygen species (ROS). However, it is imperative to determine its selectivity and standardize the components and composition of NTAPP. Here, we designed an NTAPP-generating apparatus combined with a He gas feeding system and demonstrated its high selectivity toward p53-mutated cancer cells. We first determined the proper conditions for NTAPP exposure to selectively induce apoptosis in cancer cells. The apoptotic effect of NTAPP was greater for p53-mutated cancer cells; artificial p53 expression in p53-negative HT29 cells decreased the pro-apoptotic effect of NTAPP. We also examined extra- and intracellular ROS levels in NTAPP-treated cells to deduce the mechanism of NTAPP action. While NTAPP-mediated increases in extracellular nitric oxide (NO) did not affect cell viability, intracellular ROS increased under NTAPP exposure and induced apoptotic cell death. This effect was dose-dependently reduced following treatment with ROS scavengers. NTAPP induced apoptosis even in doxorubicin-resistant cancer cell lines, demonstrating the feasibility of NTAPP as a potent cancer therapy. Collectively, these results strongly support the potential of NTAPP as a selective anticancer treatment, especially for p53-mutated cancer cells.

The Canady Helios Cold Plasma Scalpel Significantly Decreases Viability in Malignant Solid Tumor Cells in a Dose-Dependent Manner

“…Ma et al demonstrated that the effectiveness of non-thermal plasma treatment was partially dependent on p53 expression [19]. The viability of cancer cells lacking p53 was significantly reduced by non-thermal plasma treatment while p53 + cells were less affected.…”

“…An important step to make this a reality is to determine the correct dose of CAP to significantly reduce tumor cell viability. It has been reported that various cell lines react differently to CAP treatment [17][18][19][20]. Yan et al studied the reactive species consumption speed of glioblastoma U87 and breast cancers MDA-MB-231 and MCF-7, and discovered that the cancer cells that could absorb or eliminate the effective species in the media faster (glioblastoma) were more resistant to plasma-activated media than both breast cancers [17].…”

“…Naciri et al also reported that plasma sensitivity closely correlates with proliferation rates by measuring ATP levels of three cancer cell types including Chinese hamster ovary cells, osteoblast, and colon adenocarcinoma [18]. By testing eight cancerous cell lines, Ma et al claimed that p53-deficient cancer cells are more sensitive to CAP treatment due to the lack of p53-dependent cell cycle delay at G1 [19]. Therefore, the combinations of power settings and treatment times are critical to establish the correct dosage of cell line-dependent CAP treatment.…”

Actinic keratoses treated with cold atmospheric plasma

“…For example, murine models of cutaneous carcinogenesis found that bypassing the loss of INPP5A with IP6 reduced tumour formation at the initiation phase of carcinogenesis. 9 In vitro studies of other cancers, such as breast, have…”

“…3,4 Interestingly, the tumour-selectivity and apoptotic effect of CAP are especially high in p53-mutated cancer cells. 9 Dysregulation of the p53 pathway plays an important role in inducing clonal keratinocytic expansion in AK and SCC. 7 As human papilloma viruses are considered cocarcinogenic in AK and SCC development, 7 and infected keratinocytes frequently express HPV oncoproteins, virocide properties of CAP might work synergistically.…”