Reactive oxygen species from NAD(P)H:quinone oxidoreductase constitutively activate NF-κB in malignant melanoma cells

2001 ◽  
Vol 280 (3) ◽  
pp. C659-C676 ◽  
Author(s):  
Sukhdev S. Brar ◽  
Thomas P. Kennedy ◽  
A. Richard Whorton ◽  
Anne B. Sturrock ◽  
Thomas P. Huecksteadt ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Malignant Melanoma ◽  
Reactive Oxygen ◽  
Malignant Cell ◽  
Nuclear Factor Κb ◽  
Melanoma Cells ◽  
Oxygen Species ◽  
Serum Stimulation ◽  
Iκb Kinase ◽  
Transcription Factor Nuclear Factor

The transcription factor nuclear factor-κB (NF-κB) is constitutively activated in malignancies from enhanced activity of inhibitor of NF-κB (IκB) kinase, with accelerated IκBα degradation. We studied whether redox signaling might stimulate these events. Cultured melanoma cells generated superoxide anions (O[Formula: see text]) without serum stimulation. O[Formula: see text]generation was reduced by the NAD(P)H:quinone oxidoreductase (NQO) inhibitor dicumarol and the quinone analog capsaicin, suggesting that electron transfer from NQO through a quinone-mediated pathway may be an important source of endogenous reactive oxygen species (ROS) in tumor cells. Treatment of malignant melanoma cells with the H2O2 scavenger catalase, the sulfhydryl donor N-acetylcysteine, the glutathione peroxidase mimetic ebselen, or dicumarol decreased NF-κB activation. Catalase, N-acetylcysteine, ebselen, dicumarol, and capsaicin also inhibited growth of melanoma and other malignant cell lines. These results raise the possibility that ROS produced endogenously by mechanisms involving NQO can constitutively activate NF-κB in an autocrine fashion and suggest the potential for new antioxidant strategies for interruption of oxidant signaling of melanoma cell growth.

scholarly journals Melatonin Induces Melanogenesis in Human SK-MEL-1 Melanoma Cells Involving Glycogen Synthase Kinase-3 and Reactive Oxygen Species

2020 ◽  
Vol 21 (14) ◽  
pp. 4970
Author(s):  
Juan Perdomo ◽  
Carlos Quintana ◽  
Ignacio González ◽  
Inmaculada Hernández ◽  
Sara Rubio ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Glycogen Synthase ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Glycogen Synthase Kinase ◽  
Oxygen Species ◽  
Glycogen Synthase Kinase 3Β ◽  
Human Melanoma Cells

Melatonin is present in all living organisms where it displays a diversity of physiological functions. Attenuation of melanogenesis by melatonin has been reported in some mammals and also in rodent melanoma cells. However, melatonin may also stimulate melanogenesis in human melanoma cells through mechanisms that have not yet been revealed. Using the human melanoma cells SK-MEL-1 as a model, an increase in both tyrosinase activity and melanin was already observed at 24 h after melatonin treatment with maximal levels of both being detected at 72 h. This effect was associated with the induction in the expression of the enzymes involved in the synthesis of melanin. In this scenario, glycogen synthase kinase-3β seems to play a significant function since melatonin decreased its phosphorylation and preincubation with specific inhibitors of this protein kinase (lithium or BIO) reduced the expression and activity of tyrosinase. Blocking of PI3K/AKT pathway stimulated melanogenesis and the effect was suppressed by the inhibitors of glycogen synthase kinase-3β. Although melatonin is a recognized antioxidant, we found that it stimulates reactive oxygen species generation in SK-MEL-1 cells. These chemical species seem to be an important signal in activating the melanogenic process since the antioxidants N-acetyl-l-cysteine and glutathione decreased both the level and activity of tyrosinase stimulated by melatonin. Our results support the view that regulation of melanogenesis involves a cross-talk between several signaling pathways.

Toxicity assessment of metallic nickel nanoparticles in various biological models: An interplay of reactive oxygen species, oxidative stress, and apoptosis

2021 ◽  
pp. 074823372110110
Author(s):  
Shabnoor Iqbal ◽  
Farhat Jabeen ◽  
Abdul Shakoor Chaudhry ◽  
Muhammad Ajmal Shah ◽  
Gaber El-Saber Batiha
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Nickel Nanoparticles ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Volume Ratio ◽  
Nuclear Factor Κb ◽  
Metallic Nickel ◽  
Oxygen Species

Nickel nanoparticles (Ni-NPs) are widely used for multiple purposes in industries. Ni-NPs exposure is detrimental to ecosystems owing to widespread use, and so their toxicity is important to consider for real-world applications. This review mainly focuses on the notable pathophysiological activities of Ni-NPs in various research models. Ni-NPs are stated to be more toxic than bulk forms because of their larger surface area to volume ratio and are reported to provoke toxicity through reactive oxygen species generation, which leads to the upregulation of nuclear factor-κB and promotes further signaling cascades. Ni-NPs may contribute to provoking oxidative stress and apoptosis. Hypoxia-inducible factor 1α and mitogen-activated protein kinases pathways are involved in Ni-NPs associated toxicity. Ni-NPs trigger the transcription factors p-p38, p-JNK, p-ERK1/2, interleukin (IL)-3, TNF-α, IL-13, Fas, Cyt c, Bax, Bid protein, caspase-3, caspase-8, and caspase-9. Moreover, Ni-NPs have an occupational vulnerability and were reported to induce lung-related disorders owing to inhalation. Ni-NPs may cause serious effects on reproduction as Ni-NPs induced deleterious effects on reproductive cells (sperm and eggs) in animal models and provoked hormonal alteration. However, recent studies have provided limited knowledge regarding the important checkpoints of signaling pathways and less focused on the toxic limitation of Ni-NPs in humans, which therefore needs to be further investigated.

Crucial role of reactive oxygen species (ROS) for the proapoptotic effects of indirubin derivative DKP-073 in melanoma cells

2018 ◽  
Vol 58 (2) ◽  
pp. 258-269 ◽  
Author(s):  
Veselina Zhivkova ◽  
Felix Kiecker ◽  
Peter Langer ◽  
Jürgen Eberle
Keyword(s):  
Reactive Oxygen Species ◽  
Crucial Role ◽  
Reactive Oxygen ◽  
Melanoma Cells ◽  
Oxygen Species

scholarly journals Overexpression of Ras-Related C3 Botulinum Toxin Substrate 2 Radiosensitizes Melanoma Cells In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Wentao Hu ◽  
Lin Zhu ◽  
Weiwei Pei ◽  
Shuxian Pan ◽  
Ziyang Guo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Botulinum Toxin ◽  
Malignant Melanoma ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Melanoma Cells ◽  
Oxygen Species ◽  
X Rays ◽  
Nadph Oxidase Activity ◽  
Carbon Ion

Radioresistance is the major obstacle in the radiotherapy of the malignant melanoma. Thus, it is of importance to increase the radiosensitivity of melanoma cells. In the present study, the radioresistant melanoma cell line OCM-1 with inducible overexpression of Ras-related C3 botulinum toxin substrate 2 was established based on a radiation-inducible early growth response gene (Egr-1) promoter. The effects of Ras-related C3 botulinum toxin substrate 2 overexpression on the radiosensitivity of melanoma cells exposed to either X-rays or carbon ion beams were evaluated in cultured cells as well as xenograft tumor models. In addition, both reactive oxygen species yield and the NADPH oxidase activity were measured in the irradiated melanoma cells. It was found that the radiation-inducible overexpression of Ras-related C3 botulinum toxin substrate 2 sensitized the melanoma cells to both X-rays and carbon ion irradiation by enhancing the NADPH oxidase activity and the subsequent reactive oxygen species production. Besides, the overexpression of Ras-related C3 botulinum toxin substrate 2 enhanced the tumor-killing effect of radiotherapy in xenograft tumors significantly. The results of this study indicate that Ras-related C3 botulinum toxin substrate 2 is promising in increasing the radiosensitivity of melanoma cells, which provides experimental evidence and theoretical basis for clinical radiosensitization of the malignant melanoma.

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