Inhibition of Angiogenesis by Treatment with Cold Atmospheric Plasma as a Promising Therapeutic Approach in Oncology

Abstract

Background: Cold atmospheric plasma (CAP) is increasingly used in the field of oncology. Many of the mechanisms of action of CAP, such as inhibiting proliferation, DNA breakage, or the destruction of cell membrane integrity, have been investigated in many different types of tumors. In this regard, data are available from both in vivo and in vitro studies. Not only the direct treatment of a tumor but also the influence on its blood supply play a decisive role in the success of the therapy and the patient’s further prognosis. Whether the CAP influences this process is unknown, and the first indications in this regard are addressed in this study. Methods: Two different devices, kINPen and MiniJet, were used as CAP sources. Human endothelial cell line HDMEC were treated directly and indirectly with CAP, and growth kinetics were performed. To indicate apoptotic processes, caspase-3/7 assay and TUNEL assay were used. The influence of CAP on cellular metabolism was examined using the MTT and glucose assay. After CAP exposure, tube formation assay was performed to examine the capillary tube formation abilities of HDMEC and their migration was messured in separate assays. To investigate in a possible mutagenic effect of CAP treatment, a hypoxanthine-guanine-phosphoribosyl-transferase assay with non malignant cell (CCL-93) line was performed. Results: The direct CAP treatment of the HDMEC showed a robust growth-inhibiting effect, but the indirect one did not. The MMT assay showed an apparent reduction in cell metabolism in the first 24 h after CAP treatment, which appeared to normalize 48 h and 72 h after CAP application. These results were also confirmed by the glucose assay. The caspase 3/7 assay and TUNEL assay showed a significant increase in apoptotic processes in the HDMEC after CAP treatment. These results were independent of the CAP device. Both the migration and tube formation of HDMEC were significant inhibited after CAP-treatment. No malignant effects could be demonstrated by the CAP treatment on a non-malignant cell line.

The therapeutic perspective of cold atmospheric plasma in periodontal disease

“…CAP has displayed remarkable inhibitory effects on malignant tumors, and the possible mechanisms include inducing immunogenic death of tumor cells (Lin et al, 2017), preventing blood supply to the tumor (Haralambiev et al, 2020), or increasing chemotherapeutic sensitivity (Shaw et al, 2021). Likewise, CAP had effects to control oral squamous cell carcinoma by inducing Epidermal Growth Factor Receptor (EGFR) dysfunction mediated by nitric oxide radicals (J.…”

Intracellular Responses Triggered by Cold Atmospheric Plasma and Plasma-Activated Media in Cancer Cells

“…Both extrinsic and intrinsic apoptotic pathways merge at the level of death, executing enzymes—caspases 3 and 7. CAP treatment causes massive caspase 3/7 activation, cleavage, and morphological changes of cell architecture in prostate cancer LNCaP cells [ 108 , 109 ], cholangiocarcinoma cells [ 62 ], human endothelial cells HDMEC [ 113 ], and G-361 human melanoma cells. This is accompanied by increased PARP level and a blocked HGF/c-MET pathway [ 88 ].…”

Adjuvant composite cold atmospheric plasma therapy increases antitumoral effect of doxorubicin hydrochloride

“…Anti-angiogenic effects: CAP can inhibit the formation of new blood vessels (angiogenesis) that are crucial for tumor growth and metastasis. By disrupting the tumor’s blood supply, CAP can hinder its progression ( 20 ). Unlike traditional anti-cancer approaches and drugs, CAP is a selective anti-cancer treatment method.…”