Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant response
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 sh...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722001719 |
| _version_ | 1811309663420940288 |
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| author | Joey De Backer Abraham Lin Wim Vanden Berghe Annemie Bogaerts David Hoogewijs |
| author_facet | Joey De Backer Abraham Lin Wim Vanden Berghe Annemie Bogaerts David Hoogewijs |
| author_sort | Joey De Backer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T09:45:36Z |
| format | Article |
| id | doaj.art-50232330a25d4eb9af0e6a59821c5130 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-13T09:45:36Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-50232330a25d4eb9af0e6a59821c51302022-12-22T02:51:46ZengElsevierRedox Biology2213-23172022-09-0155102399Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant responseJoey De Backer0Abraham Lin1Wim Vanden Berghe2Annemie Bogaerts3David Hoogewijs4Protein 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; Corresponding author. Universiteitsplein 1, 2610, Wilrijk, Belgium.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, BelgiumProtein Chemistry, Proteomics and Epigenetic Signaling (PPES) Research Group, Department of Biomedical Sciences, University of Antwerp, BelgiumPlasma Lab for Applications in Sustainability and Medicine-Antwerp (PLASMANT) Research Group, Department of Chemistry, University of Antwerp, BelgiumSection of Medicine, Department of Endocrinology, Metabolism and Cardiovascular System, University of Fribourg, SwitzerlandMelanoma 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.http://www.sciencedirect.com/science/article/pii/S2213231722001719MelanomaCytoglobinNon-thermal plasmaROSApoptosis |
| spellingShingle | Joey De Backer Abraham Lin Wim Vanden Berghe Annemie Bogaerts David Hoogewijs Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant response Redox Biology Melanoma Cytoglobin Non-thermal plasma ROS Apoptosis |
| title | Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant response |
| title_full | Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant response |
| title_fullStr | Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant response |
| title_full_unstemmed | Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant response |
| title_short | Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant response |
| title_sort | cytoglobin inhibits non thermal plasma induced apoptosis in melanoma cells through regulation of the nrf2 mediated antioxidant response |
| topic | Melanoma Cytoglobin Non-thermal plasma ROS Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722001719 |
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