Plasma Treated Water Solutions in Cancer Treatments: The Contrasting Role of RNS

Abstract

Plasma Treated Water Solutions (PTWS) recently emerged as a novel tool for the generation of Reactive Oxygen and Nitrogen Species (ROS and RNS) in liquids. The presence of ROS with a strong oxidative power, like hydrogen peroxide (H2O2), has been proposed as the main effector for the cancer-killing properties of PTWS. A protective role has been postulated for RNS, with nitric oxide (NO) being involved in the activation of antioxidant responses and cell survival. However, recent evidences proved that NO-derivatives in proper mixtures with ROS in PTWS could enhance rather than reduce the selectivity of PTWS-induced cancer cell death through the inhibition of specific antioxidant cancer defenses. In this paper we discuss the formation of RNS in different liquids with a Dielectric Barrier Discharge (DBD), to show that NO is absent in PTWS of complex composition like plasma treated (PT)-cell culture media used for in vitro experiments, as well as its supposed protective role. Nitrite anions (NO2-) instead, present in our PTWS, were found to improve the selective death of Saos2 cancer cells compared to EA.hy926 cells by decreasing the cytotoxic threshold of H2O2 to non-toxic values for the endothelial cell line.

Selective Apoptotic Effect of Plasma Activated Liquids on Human Cancer Cell Lines

“…Furthermore, externally added H 2 O 2 was sufficient for apoptosis induction in cancer cells without any significant effect of NO 2 − (data not shown). At the studied range of concentrations of H 2 O 2 and NO 2 − , this agrees with the findings of Kurake et al [ 10 ] and Sardella et al [ 53 ], who indicated that NO 2 − at higher concentrations (H 2 O 2 : NO 2 − ratio 1:25 in [ 10 ] and 1:2 in [ 53 ]) also contributed to the selectivity of the antitumor effect of PAM. Although in the mentioned studies a higher concentration of NO 2 − than H 2 O 2 was required for the synergistic effect, in the model experiments [ 9 ] only a minimal concentration of nitrites (7.5 µM) was needed.…”

The active role of organic molecules in the formation of long‐lived reactive oxygen and nitrogen species in plasma‐treated water solutions

“…In spite of this, the concentration of NO 2 − ions in PT-cell culture media was found higher than in PT-PBS or PT-water, in each series of Figure 4, after the same − ions [31,43,44,52,52,53] plasma treatment. This difference should be related to the different chemical compositions of the liquids.…”

“…List of reactions in plasma and liquid phase involved in the formation of NO 2 − ions [ 31,43,44,52,52,53 ] …”

“…In agreement with the assumed mechanisms, hence, the production of NO 2 − ions appears strongly dependent on • NO and its derivatives in the plasma, whose formation in presence of N 2 and O 2 was assessed in our previous work. [ 44 ] In fact, the NO 2 − concentration depends on the N 2 content in the feed (Figure 4a): N 2 ‐rich plasmas (O 2 /O 2 + N 2 < 0.4) maximize the amount of NO 2 − , while O 2 ‐rich plasmas minimize it. By working in O 2 feed, in absence of N 2 , NO 2 − ions are practically absent in all PTWS (<20 µM) under investigation and no acidification of the liquids is found.…”

Patient-Derived Human Basal and Cutaneous Squamous Cell Carcinoma Tissues Display Apoptosis and Immunomodulation following Gas Plasma Exposure with a Certified Argon Jet

“…The capacity of cold physical plasma employed in medical gas plasma technology in killing tumor cells was predicted via the direct induction of ROS in tumor cells and the inhibition of tumor cells’ defense mechanism and antioxidant mechanisms [ 35 , 36 ]. This study demonstrated gas plasma-induced toxicity in vitro and in patient-derived skin cancer samples ex vivo together with immunomodulatory effects.…”