Differences in cytotoxicity induced by cold atmospheric plasma and exogenous RONS solutions on human keratinocytes and melanoma cells

In this study, we demonstrated that the widely used cold atmospheric plasma (CAP) jet could significantly inhibit the growth of melanoma cells using a contactless treatment method, The flow rate of helium gas was a key operational parameter to modulate electromagnetic (EM) effect on melanoma cells. Metal sheets with different sizes could be used as a strategy to control the strength of EM effect. More attractive, the EM effect from CAP could penetrate glass/polystyrene barriers as thick as 7 mm. All these discoveries presented the profound non-invasive nature of a physically based CAP treatment, which provided a solid foundation for CAP-based cutaneous/subcutaneous tumor therapy.

Download Full-text

Cold Atmospheric Plasma Is a Potent Tool to Improve Chemotherapy in Melanoma In Vitro and In Vivo

Biomolecules ◽

10.3390/biom10071011 ◽

2020 ◽

Vol 10 (7) ◽

pp. 1011 ◽

Cited By ~ 1

Author(s):

Mina Alimohammadi ◽

Monireh Golpour ◽

Farshad Sohbatzadeh ◽

Seyedehniaz Hadavi ◽

Sander Bekeschus ◽

...

Keyword(s):

Scientific Evidence ◽

Argon Plasma ◽

Melanoma Cells ◽

Atmospheric Plasma ◽

Tumor Control ◽

Substantial Impact ◽

L929 Cells ◽

Cold Atmospheric Plasma

Malignant melanoma is a devastating disease. Because of its aggressiveness, it also serves as a model tumor for investigating novel therapeutic avenues. In recent years, scientific evidence has shown that cold atmospheric plasma (CAP) might be a promising modality in cancer therapy. In this study, we aimed to evaluate the effect of CAP generated by an argon plasma jet alone or in combination with dacarbazine (DAC) on melanoma cells in vitro and in vivo. The effects of the CAP on inducing lipid peroxidation and nitric oxide production were higher in B16 melanoma cells in comparison to non-malignant L929 cells. Assays on cell growth, apoptosis, and expression of genes related to, e.g., autophagic processes, showed CAP to have a substantial impact in melanoma cells while there were only minoreffects in L929 cells. In vivo, both CAP monotherapy and combination with DAC significantly decreased tumor growth. These results suggest that CAP not only selectively induces cell death in melanoma but also holds promises in combination with chemotherapy that might lead to improved tumor control.

Download Full-text

Acidified Nitrite Contributes to the Antitumor Effect of Cold Atmospheric Plasma on Melanoma Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22073757 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3757

Author(s):

Tom Zimmermann ◽

Lisa A Gebhardt ◽

Lucas Kreiss ◽

Christin Schneider ◽

Stephanie Arndt ◽

...

Keyword(s):

Molecular Mechanisms ◽

Membrane Damage ◽

Melanoma Cells ◽

Atmospheric Plasma ◽

Active Components ◽

Antitumor Effects ◽

Cold Atmospheric Plasma ◽

Viability Analysis ◽

Cellular Effects ◽

The Impact

Cold atmospheric plasma (CAP) is partially ionized gas near room temperature with previously reported antitumor effects. Despite extensive research and growing interest in this technology, active components and molecular mechanisms of CAP are not fully understood to date. We used Raman spectroscopy and colorimetric assays to determine elevated nitrite and nitrate levels after treatment with a MiniFlatPlaster CAP device. Previously, we demonstrated CAP-induced acidification. Cellular effects of nitrite and strong extracellular acidification were assessed using live-cell imaging of intracellular Ca2+ levels, cell viability analysis as well as quantification of p21 and DNA damage. We further characterized these observations by analyzing established molecular effects of CAP treatment. A synergistic effect of nitrite and acidification was found, leading to strong cytotoxicity in melanoma cells. Interestingly, protein nitration and membrane damage were absent after treatment with acidified nitrite, thereby challenging their contribution to CAP-induced cytotoxicity. Further, phosphorylation of ERK1/2 was increased after treatment with both acidified nitrite and indirect CAP. This study characterizes the impact of acidified nitrite on melanoma cells and supports the importance of RNS during CAP treatment. Further, it defines and evaluates important molecular mechanisms that are involved in the cancer cell response to CAP.

Download Full-text

Use of Low Temperature Cold Atmospheric Plasma in the Treatment of Melanoma Cells

Proceedings of the 2018 8th International Conference on Bioscience, Biochemistry and Bioinformatics - ICBBB 2018 ◽

10.1145/3180382.3180389 ◽

2018 ◽

Author(s):

Pei-Ru Chen ◽

Ming-Chen Wang ◽

Yun-Ju Chuang

Keyword(s):

Low Temperature ◽

Melanoma Cells ◽

Atmospheric Plasma ◽

Cold Atmospheric Plasma

Download Full-text

Cold Atmospheric Plasma and Silymarin Nanoemulsion Activate Autophagy in Human Melanoma Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21061939 ◽

2020 ◽

Vol 21 (6) ◽

pp. 1939 ◽

Cited By ~ 6

Author(s):

Manish Adhikari ◽

Bhawana Adhikari ◽

Bhagirath Ghimire ◽

Sanjula Baboota ◽

Eun Ha Choi

Keyword(s):

Melanoma Cells ◽

Cell Number ◽

Human Melanoma ◽

Atmospheric Plasma ◽

Cold Atmospheric Plasma ◽

Human Melanoma Cells ◽

Survival Pathways ◽

Autophagy Induction ◽

The Media ◽

Intracellular Glucose

Background: Autophagy is reported as a survival or death-promoting pathway that is highly debatable in different kinds of cancer. Here, we examined the co-effect of cold atmospheric plasma (CAP) and silymarin nanoemulsion (SN) treatment on G-361 human melanoma cells via autophagy induction. Methods: The temperature and pH of the media, along with the cell number, were evaluated. The intracellular glucose level and PI3K/mTOR and EGFR downstream pathways were assessed. Autophagy-related genes, related transcriptional factors, and autophagy induction were estimated using confocal microscopy, flow cytometry, and ELISA. Results: CAP treatment increased the temperature and pH of the media, while its combination with SN resulted in a decrease in intracellular ATP with the downregulation of PI3K/AKT/mTOR survival and RAS/MEK transcriptional pathways. Co-treatment blocked downstream paths of survival pathways and reduced PI3K (2 times), mTOR (10 times), EGFR (5 times), HRAS (5 times), and MEK (10 times). CAP and SN co-treated treatment modulates transcriptional factor expressions (ZKSCAN3, TFEB, FOXO1, CRTC2, and CREBBP) and specific genes (BECN-1, AMBRA-1, MAP1LC3A, and SQSTM) related to autophagy induction. Conclusion: CAP and SN together activate autophagy in G-361 cells by activating PI3K/mTOR and EGFR pathways, expressing autophagy-related transcription factors and genes.

Download Full-text

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

Cancers ◽

10.3390/cancers11050671 ◽

2019 ◽

Vol 11 (5) ◽

pp. 671 ◽

Cited By ~ 7

Author(s):

Christin Schneider ◽

Lisa Gebhardt ◽

Stephanie Arndt ◽

Sigrid Karrer ◽

Julia L. Zimmermann ◽

...

Keyword(s):

Malignant Melanoma ◽

Melanoma Cells ◽

Reactive Species ◽

Atmospheric Plasma ◽

Protein Nitration ◽

Cold Atmospheric Plasma ◽

No Formation ◽

Anti Cancer ◽

Acidic Conditions ◽

The Impact

(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.

Download Full-text