Abstract
Breast cancer exists in multiple subtypes some of which still lack a targeted and effective therapy. Cold atmospheric plasma (CAP) has been proposed as an emerging anti-cancer treatment modality. In this study, we investigated the effects of direct and indirect CAP treatment driven by the advantageous nanosecond pulsed discharge on breast cancer cells of different malignant phenotypes and estrogen receptor (ER) status, a major factor in the prognosis and therapeutic management of breast cancer. The main CAP reactive species in liquid (i.e. H2O2, ) and gas phase were determined as a function of plasma operational parameters (i.e. treatment time, pulse voltage and frequency), while pre-treatment with the ROS scavenger NAC revealed the impact of ROS in the treatment. CAP treatment induced intense phenotypic changes and apoptosis in both ER+ and ER- cells, which is associated with the mitochondrial pathway as evidenced by the increased Bax/Bcl-2 ratio and cleavage of PARP-1. Interestingly, CAP significantly reduced CD44 protein expression (a major cancer stem cell marker and matrix receptor), while differentially affected the expression of proteases and inflammatory mediators. Collectively, the findings of the present study suggest that CAP suppresses breast cancer cell growth and regulates several effectors of the tumor microenvironment and thus it could represent an efficient therapeutic approach for distinct breast cancer subtypes.
Highlights
Breast cancer is a highly heterogeneous disease that may exist in multiple subtypes
The recorded spectrum at 31.2 kV is presented in Figure 2C revealing the major plasma species generated in the air nanosecond pulses (NSP)-dielectric barrier discharge (DBD) system of this study
Emission peaks originating from the N2 second positive system (N2 SPS) in the range 315-405 nm, the N2 first positive system (N2 FPS) between 500 and 900 nm, and N+2 at 393 and 427 nm were observed [27]
Summary
Breast cancer is a highly heterogeneous disease that may exist in multiple subtypes. Estrogen receptor alpha (ERa) expression profile is the prominent molecular feature for the discrimination of breast cancers, which are classified as ER-positive (ER+) and ER-negative (ER-). Almost 70% of breast cancers are ER+ and can be targeted with endocrine therapies. Breast cancers can be classified with regard to their extracellular matrix (ECM) expression pattern resulting in distinct ECM subtypes related with different clinical outcome [5]. Current options of breast cancer treatment include surgery, chemotherapy and radiotherapy, which all present severe limitations as they are not selective and offer incomplete tumor ablation. The development of new therapeutic approaches that would ablate incurable breast tumor subtypes is urgently needed
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