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Acidification is an Essential Process of Cold Atmospheric Plasma and Promotes the Anti-Cancer Effect on Malignant Melanoma Cells

1
Institute of Biochemistry, Emil-Fischer-Center, University of Erlangen-Nürnberg, 91054 Erlangen, Germany
2
Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany
3
Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany
4
Terraplasma medical GmbH, 85748 Garching, Germany
5
Institute of Physiology, Medical University of Vienna, 1090 Vienna, Austria
6
Comprehensive Cancer Center (CCC) Erlangen-EMN, 91054 Erlangen, Germany
*
Author to whom correspondence should be addressed.
Authors contributed equally
Cancers 2019, 11(5), 671; https://doi.org/10.3390/cancers11050671
Received: 10 April 2019 / Revised: 4 May 2019 / Accepted: 8 May 2019 / Published: 14 May 2019
PDF [1940 KB, uploaded 14 May 2019]

Abstract

(1) Background: Cold atmospheric plasma (CAP) is ionized gas near room temperature. The anti-cancer effects of CAP were confirmed for several cancer types and were attributed to CAP-induced reactive species. However, the mode of action of CAP is still not well understood. (2) Methods: Changes in cytoplasmic Ca2+ level after CAP treatment of malignant melanoma cells were analyzed via the intracellular Ca2+ indicator fura-2 AM. CAP-produced reactive species were determined by fluorescence spectroscopic and protein nitration by Western Blot analysis. (3) Results: CAP caused a strong acidification of water and solutions that were buffered with the so-called Good buffers, while phosphate-buffered solutions with higher buffer capacity showed minor pH reductions. The CAP-induced Ca2+ influx in melanoma cells was stronger in acidic pH than in physiological conditions. NO formation that is induced by CAP was dose- and pH-dependent and CAP-treated solutions only caused protein nitration in cells under acidic conditions. (4) Conclusions: We describe the impact of CAP-induced acidification on the anti-cancer effects of CAP. A synergistic effect of CAP-induced ROS, RNS, and acidic conditions affected the intracellular Ca2+ level of melanoma cells. As the microenvironment of tumors is often acidic, further acidification might be one reason for the specific anti-cancer effects of CAP.
Keywords: cold atmospheric plasma; malignant melanoma; calcium signaling; acidification; nitration cold atmospheric plasma; malignant melanoma; calcium signaling; acidification; nitration
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Schneider, C.; Gebhardt, L.; Arndt, S.; Karrer, S.; Zimmermann, J.L.; Fischer, M.J.; Bosserhoff, A.-K. Acidification is an Essential Process of Cold Atmospheric Plasma and Promotes the Anti-Cancer Effect on Malignant Melanoma Cells. Cancers 2019, 11, 671.

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