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Lin, A.; Sahun, M.; Biscop, E.; Verswyvel, H.; De Waele, J.; De Backer, J.; Theys, C.; Cuypers, B.; Laukens, K.; Berghe, W.V.; Smits, E.; Bogaerts, A. |
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Title |
Acquired non-thermal plasma resistance mediates a shift towards aerobic glycolysis and ferroptotic cell death in melanoma |
Type |
A1 Journal article |
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Year  |
2023 |
Publication |
Drug resistance updates |
Abbreviated Journal |
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Volume |
67 |
Issue |
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Pages |
100914 |
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Keywords |
A1 Journal article; Pharmacology. Therapy; ADReM Data Lab (ADReM); Center for Oncological Research (CORE); Proteinscience, proteomics and epigenetic signaling (PPES); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
To gain insights into the underlying mechanisms of NTP therapy sensitivity and resistance, using the firstever
NTP-resistant cell line derived from sensitive melanoma cells (A375).
Methods: Melanoma cells were exposed to NTP and re-cultured for 12 consecutive weeks before evaluation
against the parental control cells. Whole transcriptome sequencing analysis was performed to identify differentially
expressed genes and enriched molecular pathways. Glucose uptake, extracellular lactate, media acidification,
and mitochondrial respiration was analyzed to determine metabolic changes. Cell death inhibitors were
used to assess the NTP-induced cell death mechanisms, and apoptosis and ferroptosis was further validated via
Annexin V, Caspase 3/7, and lipid peroxidation analysis.
Results: Cells continuously exposed to NTP became 10 times more resistant to NTP compared to the parental cell
line of the same passage, based on their half-maximal inhibitory concentration (IC50). Sequencing and metabolic
analysis indicated that NTP-resistant cells had a preference towards aerobic glycolysis, while cell death analysis
revealed that NTP-resistant cells exhibited less apoptosis but were more vulnerable to lipid peroxidation and
ferroptosis.
Conclusions: A preference towards aerobic glycolysis and ferroptotic cell death are key physiological changes in
NTP-resistance cells, which opens new avenues for further, in-depth research into other cancer types. |
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Wos |
000925156500001 |
Publication Date |
2022-12-29 |
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ISSN |
1368-7646 |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
24.3 |
Times cited |
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Open Access |
OpenAccess |
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Notes |
The authors would like to thank Dr. Christophe Deben and Ms. Hannah Zaryouh (Center for Oncological Research, University of Antwerp) for the use and their help with the D300e Digital Dispenser and Spark® Cyto, as well as Ms. Rapha¨elle Corremans (Laboratory Pathophysiology, University of Antwerp) for the use of their lactate meter. The authors would also like to acknowledge the help from Ms. Tias Verhezen and Mr. Cyrus Akbari, who was involved at the start of the project but could not continue due to the COVID-19 pandemic. The authors also acknowledge the resources and services provided by the VSC (Flemish Supercomputer Center). This work was funded in part by the Research Foundation – Flanders (FWO) and the Flemish Government. The FWO fellowships and grants that funded this work also include: 12S9221N (Abraham Lin), G044420N (Abraham Lin, Annemie Bogaerts), and 1S67621N (Hanne Verswyvel). We would also like to thank several patrons, as part of this research was funded by donations from different donors, including Dedert Schilde vzw, Mr. Willy Floren, and the Vereycken family. We would also like to acknowledge the support from the European Cooperation in Science & Technology (COST) Action on Therapeutical applications of Cold Plasmas (CA20114; PlasTHER). |
Approved |
Most recent IF: 24.3; 2023 IF: 10.906 |
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Call Number |
PLASMANT @ plasmant @c:irua:193167 |
Serial |
7240 |
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Author |
Lin, A.; Biscop, E.; Gorbanev, Y.; Smits, E.; Bogaerts, A. |
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Title |
Toward defining plasma treatment dose : the role of plasma treatment energy of pulsed‐dielectric barrier discharge in dictating in vitro biological responses |
Type |
A1 Journal article |
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Year |
2022 |
Publication |
Plasma Processes And Polymers |
Abbreviated Journal |
Plasma Process Polym |
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Volume |
19 |
Issue |
3 |
Pages |
e2100151 |
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Keywords |
A1 Journal article; Pharmacology. Therapy; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT) |
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Abstract |
The energy dependence of a pulsed-dielectric barrier discharge (DBD) plasma treatment on chemical species production and biological responses was investigated. We hypothesized that the total plasma energy delivered during treatment encompasses the influence of major application parameters. A microsecond-pulsed DBD system was used to treat three different cancer cell lines and cell viability was analyzed. The energy per pulse was measured and the total plasma treatment energy was controlled by adjusting the pulse frequency, treatment time, and application distance. Our data suggest that the delivered plasma energy plays a predominant role in stimulating a biological response in vitro. This study aids in developing steps toward defining a plasma treatment unit and treatment dose for biomedical and clinical research. |
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Wos |
000711907800001 |
Publication Date |
2021-10-28 |
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ISSN |
1612-8850 |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
3.5 |
Times cited |
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Open Access |
OpenAccess |
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Notes |
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Approved |
Most recent IF: 3.5 |
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Call Number |
UA @ admin @ c:irua:182916 |
Serial |
7219 |
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Author |
Lin, A.; Biscop, E.; Breen, C.; Butler, S.J.; Smits, E.; Bogaerts, A.; Jakovljevic, V. |
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Title |
Critical Evaluation of the Interaction of Reactive Oxygen and Nitrogen Species with Blood to Inform the Clinical Translation of Nonthermal Plasma Therapy |
Type |
A1 Journal article |
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Year |
2020 |
Publication |
Oxidative Medicine And Cellular Longevity |
Abbreviated Journal |
Oxid Med Cell Longev |
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2020 |
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Pages |
1-10 |
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Keywords |
A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE) |
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Abstract |
Non-thermal plasma (NTP), an ionized gas generated at ambient pressure and temperature, has been an emerging technology for medical applications. Through controlled delivery of reactive oxygen and nitrogen species (ROS/RNS), NTP can elicit hormetic cellular responses, thus stimulating broad therapeutic effects. To enable clinical translation of the promising preclinical research into NTP therapy, a deeper understanding of NTP interactions with clinical substrates is profoundly needed. Since NTP-generated ROS/RNS will inevitably interact with blood in several clinical contexts, understanding their stability in this system is crucial. In this study, two medically relevant NTP delivery modalities were used to assess the stability of NTP-generated ROS/RNS in three aqueous solutions with increasing organic complexities: phosphate-buffered saline (PBS), blood plasma (BP), and processed whole blood. NTP-generated RNS collectively (NO2−, ONOO−), H2O2, and ONOO− exclusively were analyzed over time. We demonstrated that NTP-generated RNS and H2O2 were stable in PBS but scavenged by different components of the blood. While RNS remained stable in BP after initial scavenging effects, it was completely reduced in processed whole blood. On the other hand, H2O2 was completely scavenged in both liquids over time. Our previously developed luminescent probe europium(III) was used for precision measurement of ONOO− concentration. NTP-generated ONOO− was detected in all three liquids for up to at least 30 seconds, thus highlighting its therapeutic potential. Based on our results, we discussed the necessary considerations to choose the most optimal NTP modality for delivery of ROS/RNS to and via blood in the clinical context. |
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Wos |
000600343500001 |
Publication Date |
2020-12-03 |
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ISSN |
1942-0900 |
ISBN |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
4.593 |
Times cited |
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Open Access |
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Notes |
This work was supported in part by the Research Foundation Flanders grant 12S9218N (A.L.) ,12S9221N (A.L) and G044420N (A.B. and A.L). This work was also supported by the Methusalem grant (A.B.). |
Approved |
Most recent IF: NA |
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Call Number |
PLASMANT @ plasmant @c:irua:174000 |
Serial |
6658 |
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