Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant response

Backer, Joey De; Lin, Abraham; Berghe, Wim Vanden; Bogaerts, Annemie; Hoogewijs, David

doi:10.1016/j.redox.2022.102399

Cited by 10 publications

(5 citation statements)

References 80 publications

(96 reference statements)

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“…Intriguingly, the knockdown of CYGB also affected NRF2 and HO-1 protein expression under basal conditions ( Figure S3 ). This is in accordance with previous studies [ 14 , 39 , 40 , 41 ] and is consistent with results obtained recently by our group [ 31 ]. Considering NRF2’s central role in heme biosynthesis, and taking into account CYGB as a heme-containing protein, cells possessing abundant endogenous CYGB levels constitutively induce NRF2 protein, and subsequently HO-1 [ 42 , 43 ].…”

Section: Discussionsupporting

confidence: 94%

“…Differential analysis of normalized counts using DESeq2 identified 316 genes that were differentially expressed under basal conditions. Of those 316 genes, 111 genes were differentially expressed above an absolute log 2 fold change of 1 (DEGs) (see [ 31 ] for more details).…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, MEG3 was one of the DEGs identified to be dramatically downregulated in G361-shCYGB cells upon RSL3 treatment ( Figure 7 A) and was recently found to also be downregulated under basal conditions [ 31 ]. Furthermore, MEG3 was shown to inhibit tumor formation, growth and metastasis in melanoma [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

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Cytoglobin Silencing Promotes Melanoma Malignancy but Sensitizes for Ferroptosis and Pyroptosis Therapy Response

et al. 2022

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Despite recent advances in melanoma treatment, there are still patients that either do not respond or develop resistance. This unresponsiveness and/or acquired resistance to therapy could be explained by the fact that some melanoma cells reside in a dedifferentiated state. Interestingly, this dedifferentiated state is associated with greater sensitivity to ferroptosis, a lipid peroxidation-reliant, iron-dependent form of cell death. Cytoglobin (CYGB) is an iron hexacoordinated globin that is highly enriched in melanocytes and frequently downregulated during melanomagenesis. In this study, we investigated the potential effect of CYGB on the cellular sensitivity towards (1S, 3R)-RAS-selective lethal small molecule (RSL3)-mediated ferroptosis in the G361 melanoma cells with abundant endogenous expression. Our findings show that an increased basal ROS level and higher degree of lipid peroxidation upon RSL3 treatment contribute to the increased sensitivity of CYGB knockdown G361 cells to ferroptosis. Furthermore, transcriptome analysis demonstrates the enrichment of multiple cancer malignancy pathways upon CYGB knockdown, supporting a tumor-suppressive role for CYGB. Remarkably, CYGB knockdown also triggers activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and subsequent induction of pyroptosis target genes. Altogether, we show that silencing of CYGB expression modulates cancer therapy sensitivity via regulation of ferroptosis and pyroptosis cell death signaling pathways.

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Section: Discussionsupporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

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Cytoglobin Silencing Promotes Melanoma Malignancy but Sensitizes for Ferroptosis and Pyroptosis Therapy Response

et al. 2022

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“…Plasma-treated lysozyme has been shown to induce apoptosis of cancer cells [ 78 ]. Furthermore, structural modifications of cytoglobin have been reported to impair its protective activity against NTP-induced oxidative stress in melanoma cells [ 79 ].…”

Section: Anti-cancer Therapiesmentioning

confidence: 99%

Non-Thermal Plasma Application in Medicine—Focus on Reactive Species Involvement

Moszczyńska

Roszek

Wiśniewski

2023

IJMS

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Non-thermal plasma (NTP) application in medicine is a dynamically developing interdisciplinary field. Despite the fact that basics of the plasma phenomenon have been known since the 19th century, growing scientific attention has been paid in recent years to the use of plasma in medicine. Three most important plasma-based effects are pivotal for medical applications: (i) inactivation of a broad spectrum of microorganisms, (ii) stimulation of cell proliferation and angiogenesis with lower plasma treatment intensity, and (iii) inactivation of cells by initialization of cell death with higher plasma intensity. In this review, we explain the underlying chemical processes and reactive species involvement during NTP in human (or animal) tissues, as well as in bacteria inactivation, which leads to sterilization and indirectly supports wound healing. In addition, plasma-mediated modifications of medical surfaces, such as surgical instruments or implants, are described. This review focuses on the existing knowledge on NTP-based in vitro and in vivo studies and highlights potential opportunities for the development of novel therapeutic methods. A full understanding of the NTP mechanisms of action is urgently needed for the further development of modern plasma-based medicine.

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“…Non-thermal plasma (NTP) is an ionized gas composed of charged particles, electronically excited atoms, molecules, free radicals, and ultraviolet photons [ 1 ]. NTP is believed to generate reactive oxygen species (ROS) that trigger DNA damage and mitochondrial dysfunction and inhibit tumor cell metabolism, thereby inducing tumor cell death [ 2 , 3 ]. Several studies have shown that NTP exhibits antitumor activity against various cancers, such as colorectal cancer, leukemia, and mesothelioma [ [4] , [5] , [6] ].…”

Section: Introductionmentioning

confidence: 99%

Non-thermal plasma-treated melatonin inhibits the biological activity of HCC cells by increasing intracellular ROS levels and reducing RRM2 expression

Chen

Jin

et al. 2023

Heliyon

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Cytoglobin inhibits non-thermal plasma-induced apoptosis in melanoma cells through regulation of the NRF2-mediated antioxidant response

Cited by 10 publications

References 80 publications

Cytoglobin Silencing Promotes Melanoma Malignancy but Sensitizes for Ferroptosis and Pyroptosis Therapy Response

Cytoglobin Silencing Promotes Melanoma Malignancy but Sensitizes for Ferroptosis and Pyroptosis Therapy Response

Non-Thermal Plasma Application in Medicine—Focus on Reactive Species Involvement

Non-thermal plasma-treated melatonin inhibits the biological activity of HCC cells by increasing intracellular ROS levels and reducing RRM2 expression

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