Faculty of Medicine, Institute of Biophysics, University of Coimbra, 3000-548 Coimbra, Portugal.
Faculty of Medicine, Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), University of Coimbra, 3000-548 Coimbra, Portugal.
Int J Mol Sci. 2022 Feb 1;23(3):1698. 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.
乳腺癌（BC）是一种恶性肿瘤，在全球范围内女性的发病率和死亡率最高。目前的治疗方法包括手术、放疗和化疗，在某些情况下还包括靶向治疗。然而，这些治疗方法通常伴随着严重的不良反应。为了寻找治疗乳腺癌的新方法，我们评估了冷等离体（CAP）在两种具有不同组织学特征的细胞系（MCF7 和 HCC1806）中的治疗潜力。细胞凋亡似乎是最常见的死亡类型，这得到了几种生化特征的证实，包括磷脂酰丝氨酸暴露、线粒体膜电位破坏、BAX/BCL2 比值增加和原胱天蛋白酶 3 丢失。此外，细胞周期 G2/M 期的细胞积累表明复制能力丧失和存活能力下降。尽管有报道称在暴露于等离子体的培养基中存在过氧化物体积分数中毒的浓度，但在两种细胞系中，细胞内过氧化物浓度在等离子体暴露后不久就会总体下降，同时 GSH 水平也会下降。在 HCC1806 中，一氧化氮（NO）浓度升高伴随着超氧化物水平降低，这表明这些细胞能够将等离子体衍生的亚硝酸盐转化为 NO，与超氧化物歧化酶（SOD）竞争超氧化物形成过氧亚硝酸盐。在 CAP 治疗期间，细胞抗氧化活性的同时抑制，特别是用叠氮化钠抑制细胞色素 c 氧化酶，协同增加了等离子体的毒性。因此，这项体外研究阐明了 CAP 在乳腺癌治疗中的治疗潜力，阐明了其可能的作用机制。
