Cold Atmospheric Plasma and Plasma-Activated Medium Trigger RONS-Based Tumor Cell Apoptosis.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Culture Media* ; Plasma Gases*; Apoptosis/*drug effects ; Reactive Nitrogen Species/*pharmacology ; Reactive Oxygen Species/*pharmacology; Aquaporins/metabolism ; Caspase 8/metabolism ; Catalase/metabolism ; Cell Line, Tumor/drug effects ; Cell Membrane/metabolism ; Glutathione/metabolism ; Humans ; Hydrogen Peroxide/metabolism ; Lipid Peroxidation ; NADPH Oxidase 1/antagonists & inhibitors ; NADPH Oxidase 1/metabolism ; Neoplasm Proteins/metabolism ; Nitrites/metabolism ; Peroxynitrous Acid/metabolism ; RNA Interference ; RNA, Small Interfering/pharmacology ; Reactive Nitrogen Species/metabolism ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/metabolism

The selective in vitro anti-tumor mechanisms of cold atmospheric plasma (CAP) and plasma-activated media (PAM) follow a sequential multi-step process. The first step involves the formation of primary singlet oxygen ( ¹ O 2 ) through the complex interaction between NO 2 ^- and H 2 O 2. ¹ O 2 then inactivates some membrane-associated catalase molecules on at least a few tumor cells. With some molecules of their protective catalase inactivated, these tumor cells allow locally surviving cell-derived, extracellular H 2 O 2 and ONOO ^─ to form secondary ¹ O 2 . These species continue to inactivate catalase on the originally triggered cells and on adjacent cells. At the site of inactivated catalase, cell-generated H 2 O 2 enters the cell via aquaporins, depletes glutathione and thus abrogates the cell's protection towards lipid peroxidation. Optimal inactivation of catalase then allows efficient apoptosis induction through the HOCl signaling pathway that is finalized by lipid peroxidation. An identical CAP exposure did not result in apoptosis for nonmalignant cells. A key conclusion from these experiments is that tumor cell-generated RONS play the major role in inactivating protective catalase, depleting glutathione and establishing apoptosis-inducing RONS signaling. CAP or PAM exposure only trigger this response by initially inactivating a small percentage of protective membrane associated catalase molecules on tumor cells.

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0 (Aquaporins)
0 (Culture Media)
0 (Neoplasm Proteins)
0 (Nitrites)
0 (Plasma Gases)
0 (RNA, Small Interfering)
0 (Reactive Nitrogen Species)
0 (Reactive Oxygen Species)
14691-52-2 (Peroxynitrous Acid)
BBX060AN9V (Hydrogen Peroxide)
EC 1.11.1.6 (CAT protein, human)
EC 1.11.1.6 (Catalase)
EC 1.15.1.1 (Superoxide Dismutase)
EC 1.6.3.- (NADPH Oxidase 1)
EC 1.6.3.- (NOX1 protein, human)
EC 3.4.22.- (CASP8 protein, human)
EC 3.4.22.- (Caspase 8)
GAN16C9B8O (Glutathione)

Date Created: 20191004 Date Completed: 20201109 Latest Revision: 20210110

20231215

PMC6775051

10.1038/s41598-019-50291-0

31578342