Breast cancer (BC) is a malignant neoplasia with the highest incidence and mortality rates in women worldwide. Currently, therapies include surgery, radiotherapy, and chemotherapy, including targeted therapies in some cases. However, treatments are often associated with serious adverse effects. Looking for new options in BC treatment, we evaluated the therapeutic potential of cold atmospheric plasma (CAP) in two cell lines (MCF7 and HCC1806) with distinct histological features. Apoptosis seemed to be the most prevalent type of death, as corroborated by several biochemical features, including phosphatidylserine exposure, the disruption of mitochondrial membrane potential, an increase in BAX/BCL2 ratio and procaspase 3 loss. Moreover, the accumulation of cells in the G2/M phase of the cell cycle points to the loss of replication ability and decreased survival. Despite reported toxic concentrations of peroxides in culture media exposed to plasma, intracellular peroxide concentration was overall decreased accompanying a reduction in GSH levels shortly after plasma exposure in both cell lines. In HCC1806, elevated nitric oxide (NO) concentration accompanied by reduced superoxide levels suggests that these cells are capable of converting plasma-derived nitrites into NO that competes with superoxide dismutase (SOD) for superoxide to form peroxinitrite. The concomitant inhibition of the antioxidative activity of cells during CAP treatment, particularly the inhibition of cytochrome c oxidase with sodium azide, synergistically increased plasma toxicity. Thus, this in vitro research enlightens the therapeutic potential of CAP in the treatment of breast cancer, elucidating its possible mechanisms of action.

The need for effective and safe therapies for cancer is growing as aging is modifying its epidemiology. Cold atmospheric plasma (CAP) has gained attention as a potential anti-tumor therapy. CAP is a gas with enough energy to ionize a significant fraction of its constituent particles, forming equal numbers of positive ions and electrons. Timely-resolved output voltage measurement, emission spectroscopy, and quantification of reactive species (RS) in plasma-activated media (PAM) were performed to characterize the physical and chemical properties of plasma. To assess the cytotoxicity of cold atmospheric plasma in human tumors, different cell lines were cultured, plated, and exposed to CAP, followed by MTT and SRB colorimetric assays 24 h later. Human fibroblasts, phenotypically normal cells, were processed similarly. Plasma cytotoxicity was higher in cells of breast cancer, urinary bladder cancer, osteosarcoma, lung cancer, melanoma, and endometrial cancer. Cytotoxicity was time-dependent and possibly related to the increased production of hydrogen peroxide in the exposed medium. Sixty seconds of CAP exposure renders selective effects, preserving the viability of fibroblast cells. These results point to the importance of conducting further studies of the therapy with plasma.

Breast cancer is a growing disease, with a high worldwide incidence and mortality rate among women. Among the various types, the treatment of triple-negative breast cancer (TNBC) remains a challenge. Considering the recent advances in cold atmospheric plasma (CAP) cancer research, our goal was to evaluate efficacy data from studies based on chemotherapy and CAP in TNBC cell lines and animal models. A search of the literature was carried out in the PubMed, Web of Science, Cochrane Library, and Embase databases. Of the 10,999 studies, there were fifty-four in vitro studies, three in vivo studies, and two in vitro and in vivo studies included. MDA-MB-231 cells were the most used. MTT, MTS, SRB, annexin-V/propidium iodide, trypan blue, and clonogenic assay were performed to assess efficacy in vitro, increasing the reliability and comprehensiveness of the data. There was found to be a decrease in cell proliferation after both chemotherapy and CAP; however, different protocol settings, including an extensive range of drug doses and CAP exposure times, were reported. For both therapies, a considerable reduction in tumor volume was observed in vivo compared with that of the untreated group. The treatment of TNBC cell lines with CAP proved successful, with apoptosis emerging as the predominant type of cellular death. This systematic review presents a comprehensive overview of the treatment landscape in chemotherapy and CAP regarding their efficacy in TNBC cell lines.

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.