PMID- 35850009
OWN - NLM
STAT- Publisher
LR  - 20231019
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 55
DP  - 2022 Sep
TI  - Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells 
      through regulation of the NRF2-mediated antioxidant response.
PG  - 102399
LID - S2213-2317(22)00171-9 [pii]
LID - 10.1016/j.redox.2022.102399 [doi]
LID - 102399
AB  - Melanoma arises from pigment-producing cells called melanocytes located in the 
      basal layers of the epidermis of the skin. Cytoglobin (CYGB) is a ubiquitously 
      expressed hexacoordinated globin that is highly enriched in melanocytes and 
      frequently downregulated during melanomagenesis. Previously, we showed that 
      non-thermal plasma (NTP)-produced reactive oxygen and nitrogen species (RONS) 
      lead to the formation of an intramolecular disulfide bridge that would allow CYGB 
      to function as a redox-sensitive protein. Here, we investigate the cytotoxic 
      effect of indirect NTP treatment in two melanoma cell lines with divergent 
      endogenous CYGB expression levels, and we explore the role of CYGB in determining 
      treatment outcome. Our findings are consistent with previous studies supporting 
      that NTP cytotoxicity is mediated through the production of RONS and leads to 
      apoptotic cell death in melanoma cells. Furthermore, we show that NTP-treated 
      solutions elicit an antioxidant response through the activation of nuclear factor 
      erythroid 2-related factor 2 (NRF2). The knockdown and overexpression of CYGB 
      respectively sensitizes and protects melanoma cells from RONS-induced apoptotic 
      cell death. The presence of CYGB enhances heme-oxygenase 1 (HO-1) and NRF2 
      protein expression levels, whereas the absence impairs their expression. 
      Moreover, analysis of the CYGB-dependent transcriptome demonstrates the tumor 
      suppressor long non-coding RNA maternally expressed 3 (MEG3) as a hitherto 
      undescribed link between CYGB and NRF2. Thus, the presence of CYGB, at least in 
      melanoma cells, seems to play a central role in determining the therapeutic 
      outcome of RONS-inducing anticancer therapies, like NTP-treated solutions, 
      possessing both tumor-suppressive and oncogenic features. Hence, CYGB expression 
      could be of interest either as a biomarker or as a candidate for future targeted 
      therapies in melanoma.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - De Backer, Joey
AU  - De Backer J
AD  - Protein Chemistry, Proteomics and Epigenetic Signaling (PPES) Research Group, 
      Department of Biomedical Sciences, University of Antwerp, Belgium; Section of 
      Medicine, Department of Endocrinology, Metabolism and Cardiovascular System, 
      University of Fribourg, Switzerland. Electronic address: 
      Joey.debacker@uantwerpen.be.
FAU - Lin, Abraham
AU  - Lin A
AD  - Plasma Lab for Applications in Sustainability and Medicine-Antwerp (PLASMANT) 
      Research Group, Department of Chemistry, University of Antwerp, Belgium; Center 
      for Oncological Research (CORE), Integrated Personalized & Precision Oncology 
      Network (IPPON), University of Antwerp, Belgium.
FAU - Berghe, Wim Vanden
AU  - Berghe WV
AD  - Protein Chemistry, Proteomics and Epigenetic Signaling (PPES) Research Group, 
      Department of Biomedical Sciences, University of Antwerp, Belgium.
FAU - Bogaerts, Annemie
AU  - Bogaerts A
AD  - Plasma Lab for Applications in Sustainability and Medicine-Antwerp (PLASMANT) 
      Research Group, Department of Chemistry, University of Antwerp, Belgium.
FAU - Hoogewijs, David
AU  - Hoogewijs D
AD  - Section of Medicine, Department of Endocrinology, Metabolism and Cardiovascular 
      System, University of Fribourg, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20220714
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
SB  - IM
PMC - PMC9294208
OTO - NOTNLM
OT  - Apoptosis
OT  - Cytoglobin
OT  - Melanoma
OT  - Non-thermal plasma
OT  - ROS
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2022/07/20 06:00
MHDA- 2022/07/20 06:00
PMCR- 2022/07/14
CRDT- 2022/07/19 07:15
PHST- 2022/06/25 00:00 [received]
PHST- 2022/07/05 00:00 [accepted]
PHST- 2022/07/20 06:00 [pubmed]
PHST- 2022/07/20 06:00 [medline]
PHST- 2022/07/19 07:15 [entrez]
PHST- 2022/07/14 00:00 [pmc-release]
AID - S2213-2317(22)00171-9 [pii]
AID - 102399 [pii]
AID - 10.1016/j.redox.2022.102399 [doi]
PST - ppublish
SO  - Redox Biol. 2022 Sep;55:102399. doi: 10.1016/j.redox.2022.102399. Epub 2022 Jul 
      14.