Abstract
Reactive nitrogen species (RNS), including nitric oxide (NO·) has been known as one of the key regulatory molecules in the immune system. In this study, we generated RNS-containing water treated with microwave plasma-generated gas in which the major component was nitric oxide (PGNO), and the effect on the macrophage polarization was investigated. The RNS-containing water was diluted in complete cell culture media (PGNO-solution) into the concentration that did not induce cell death in RAW 264.7 murine macrophages. PGNO-solution upregulates M1-type macrophage activation and downregulates the characteristics of M2-type macrophage at the transcriptional level. In addition, the PGNO-solution-treated M2-like macrophages had higher potential in killing melanoma cells. The anticancer potential was also investigated in a syngeneic mouse model. Our results show that PGNO-solution has the potential to convert the fate of macrophages, suggesting PGNO-solution treatment as a supportive method for controlling the function of macrophages under the tumor microenvironment.
Highlights
Plasma-activated water (PAW) or media (PAM) has been introduced as an effective solution in killing various kinds of cancer cells, including ovarian cancer, cervical cancer, pancreatic cancer and glioblastoma [1,2,3,4,5,6]
PAM does not have any possibility of electrical hazards, it can be stored at low temperature for a certain period, and it can be injected into any part of the body
Since PAM contains relatively long-lived reactive species compared to direct plasma treatment, hydrogen peroxide and nitric oxide ions were identified as the main players in PAM reactivity [7,8,9,10,11,12,13,14,15,16]
Summary
Plasma-activated water (PAW) or media (PAM) has been introduced as an effective solution in killing various kinds of cancer cells, including ovarian cancer, cervical cancer, pancreatic cancer and glioblastoma [1,2,3,4,5,6]. It is well known that cancer cells create microenvironments that support their growth and suppress antitumor immune activities. It is typically characterized by low oxygen, low pH, high lactate, high RNS, etc., which results in differentiated responses of cellular components [21]. We generated RNS-containing water treated with microwave plasma-generated gas in which the major component was nitric oxide (PGNO) and investigated its effects on the anticancer effect of macrophages in vitro and in vivo [31,32,33]. The effects of RNS-containing PAW on tumor immunity were discussed
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