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
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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.
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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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