Cold atmospheric plasma induces apoptosis of melanoma cells via Sestrin2-mediated nitric oxide synthase signaling.

Abstract

Cold atmospheric plasma (CAP) represents a promising therapy for selectively cancer killing. However, the mechanism of CAP-induced cancer cell death remains unclear. Here, we identified the tumor necrosis factor-family members, especially Fas, and overloaded intracellular nitric oxide participated in CAP induced apoptosis in A375 and A875 melanoma cell lines, which was known as extrinsic apoptosis pathway. This progress was mediated by antagonistic protein of reactive oxygen species, Sestrin2. The over expression of Sestrin2 induced by plasma treatment resulted in phosphorylation of p38 mitogen-activated protein kinase (MAPK), followed by increased expression of nitric oxide synthase (iNOS), Fas and Fas ligand. Depletion of Sestrin2 reduced iNOS and Fas expression, which was associated with reduction of plasma-induced apoptosis. In contrast, inhibition of iNOS activity and phosphorylation of p38 did not alter Sestrin2 expression in plasma-treated melanoma cells. Taken together, cold atmospheric plasma increases Sestrin2 expression and further activates downstream iNOS, Fas and p38 MAPK signaling to induce apoptosis of melanoma cell lines. These findings suggest a previously unrecognized mechanism in melanoma cells response to cold atmospheric plasma therapy.

• Authors: Jun Xia, Weihui Zeng, Yumin Xia, Bingchuan Wang, Dehui Xu, Dingxin Liu, Michael G Kong, Yingying Dong
• Journal: Journal of biophotonics (J Biophotonics) Vol. 12 Issue 1 Pg. e201800046 (01 2019) ISSN: 1864-0648 [Electronic] Germany
• PMID: 29931745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Nuclear Proteins
• Plasma Gases
• SESN2 protein, human
• Nitric Oxide
• Nitric Oxide Synthase
• p38 Mitogen-Activated Protein Kinases

Topics

• Apoptosis (drug effects)
• Atmosphere (chemistry)
• Cell Line, Tumor
• Cold Temperature
• Humans
• MAP Kinase Signaling System (drug effects)
• Melanoma (pathology)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase (metabolism)
• Nuclear Proteins (metabolism)
• Plasma Gases (pharmacology)
• p38 Mitogen-Activated Protein Kinases (metabolism)