# Is Cold Atmospheric Plasma Selective for Breast Tumor Cells? A Systematic Review

## TL;DR

This systematic review explores whether cold atmospheric plasma selectively targets breast cancer cells over nonmalignant cells in laboratory studies.

## Contribution

The study systematically evaluates the selectivity of cold atmospheric plasma and plasma-activated solutions for breast cancer cells in vitro.

## Key findings

- CAP and PAS reduced cancer cell viability with less damage to nonmalignant cells, suggesting partial selectivity.
- Elevated ROS levels in cancer cells may contribute to their increased vulnerability to CAP/PAS treatments.
- CAP treatment also reduced breast cancer cell migration and enhanced the effectiveness of other therapies.

## Abstract

Breast cancer (BC) is the most diagnosed cancer among women and ranks as the fourth leading cause of cancer-related deaths worldwide. Current main treatments have significant issues, including a lack of selectivity for tumor cells. Over the past decade, cold atmospheric plasma (CAP) has been examined as possible therapy for cancer. Therefore, this systematic review aimed to understand if there is selectivity of CAP or plasma-activated solutions (PAS) for BC cell lines in vitro. The research in PubMed, Embase, Web of Science, and Cochrane databases resulted in 243 articles, and of these, 32 in vitro studies were included. MDA-MB-231 and MCF-10A cells were the most used. MTT, MTS, SRB, trypan blue, clonogenic, resazurin, luciferin, annexin-V/propidium iodide, reactive oxygen species (ROS), and scratch assays were carried out. This research showed that CAP and PAS tended to reduce the viability of cancer cells, causing less damage to nonmalignant cells, demonstrating selective or partial selectivity toward cancer cells. One of the mechanisms potentially underlying this selectivity is the elevated ROS basal levels typically found in cancer cells. These high ROS levels may lead to increased expression of membrane aquaporins and a reduced capacity for antioxidant defense, contributing to heightened membrane permeability and vulnerability to oxidative damage. Additionally, the treatments also tended to reduce the migration of BC cells. CAP treatment enhanced several other therapies’ effectiveness. However, the differences in experimental protocols, treatment approaches, equipment features, and exposure times observed across the studies made it impossible to carry out the planned meta-analysis. Existing in vitro evidence indicates that CAP/PAS exhibit partial selectivity for breast cancer cells, but due to the heterogeneity in experimental protocols, the consistency of selectivity remains to be verified. Further research is needed to elucidate their mechanisms of action and to standardize experimental methods.