Cold Atmospheric Plasma Apoptotic and Oxidative Effects on MCF7 and HCC1806 Human Breast Cancer Cells

• Published in: International journal of molecular sciences Vol. 23; no. 3; p. 1698
• Main Authors: Almeida-Ferreira, Catarina, Silva-Teixeira, Rafael, Gonçalves, Ana Cristina, Marto, Carlos Miguel, Sarmento-Ribeiro, Ana Bela, Caramelo, Francisco, Botelho, Maria Filomena, Laranjo, Mafalda
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-02-2022; MDPI
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Atmospheric pressure; Breast cancer; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - physiopathology; Cancer therapies; Cell culture; Cell cycle; Cell Line, Tumor; Chemotherapy; Cold; cold atmospheric plasma; Culture media; Cytochrome-c oxidase; Exposure; Humans; Kinases; MCF-7 Cells; Membrane potential; Membrane Potential, Mitochondrial; Mitochondria; Nitric oxide; Oxidative Stress; Peroxides; Phosphatidylserine; Plasma; plasma gases; Plasma Gases - pharmacology; Plasma Gases - therapeutic use; Radiation therapy; reactive nitrogen species; Reactive Oxygen Species; Superoxide dismutase; Toxicity; reactive nitrogen species; cold atmospheric plasma; breast neoplasms; reactive oxygen species; plasma gases
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031698

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.