scholarly journals Frugoside Induces Mitochondria-Mediated Apoptotic Cell Death through Inhibition of Sulfiredoxin Expression in Melanoma Cells

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 854 ◽  
Author(s):  
Song ◽  
Jeong ◽  
Kim ◽  
Shin ◽  
Jang
Keyword(s):  
Cell Death ◽  
Antitumor Effect ◽  
Apoptotic Cell ◽  
Bioactive Compound ◽  
Melanoma Cells ◽  
Therapeutic Agents ◽  
Human Melanoma ◽  
Oxygen Species ◽  
Therapeutic Implications ◽  
Life Threatening

Malignant melanoma is the most life-threatening neoplasm of the skin. Despite the increase in incidence, melanoma is becoming more resistant to current therapeutic agents. The bioactive compound frugoside has been recently reported to inhibit growth when used in various cancer cells. However, this effect has not been demonstrated in melanoma. Here, we found that frugoside inhibited the rate of reduction of hyperoxidized peroxiredoxins (Prxs) by downregulating sulfiredoxin (Srx) expression. Furthermore, frugoside increased the accumulation of sulfinic Prxs and reactive oxygen species (ROS) and stimulated p-p38 activation, resulting in the mitochondria-mediated death of M14 and A375 human melanoma cells. The mitochondria-mediated cell death induced by frugoside was inhibited by the overexpression of Srx and antioxidants, such as N-acetyl cysteine and diphenyleneiodonium. In addition, we observed that frugoside inhibited tumor growth without toxicity through a M14 xenograft animal model. Taken together, our findings reveal that frugoside exhibits a novel antitumor effect based on a ROS-mediated cell death in melanoma cells, which may have therapeutic implications.

Ursolic acid induced apoptotic cell death following activation of caspases in isolated human melanoma cells

2014 ◽  
Vol 39 (2) ◽  
pp. 230-236 ◽  
Author(s):  
Mahmoud Mahmoudi ◽  
Shahrzad Zamani Taghizadeh Rabe ◽  
Mahdi Balali-Mood ◽  
Gholamreza Karimi ◽  
Nafiseh Tabasi ◽  
...  
Keyword(s):  
Cell Death ◽  
Ursolic Acid ◽  
Apoptotic Cell ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Apoptotic Cell Death ◽  
Human Melanoma Cells

scholarly journals Antifungal Agents Induce Apoptotic and Non‐Apoptotic Cell Death in Human Melanoma Cells

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
David W Koh ◽  
Anna H Eskender ◽  
Ayah T Daghistani ◽  
Lukas R Jira ◽  
Shelby G McKamey
Keyword(s):  
Cell Death ◽  
Antifungal Agents ◽  
Apoptotic Cell ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Apoptotic Cell Death ◽  
Human Melanoma Cells

scholarly journals Transcriptional network constituted of CBP, Ku70, NOX2, and BAX prevents the cell death of necrosis, paraptosis, and apoptosis in human melanoma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Liang Ding ◽  
Yalei Wen ◽  
Xin Zhang ◽  
Fang Zhao ◽  
Kenao Lv ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Human Melanoma ◽  
Transcriptional Network ◽  
Multiple Roles ◽  
Creb Binding Protein ◽  
Cycle Arrest ◽  
Intracellular Ros ◽  
High Level

AbstractCREB-binding protein (CBP) is an acetyltransferase known to play multiple roles in the transcriptions of genes involving oxidative metabolism, cell cycle, DNA damage checkpoints, and cell death. In this study, CBP was found to positively regulate the expression of Ku70, and both CBP and Ku70 were found to negatively regulate the expression of NOX2, therefore, mitigating the intracellular ROS in human melanoma. Knocking down CBP or Ku70 induced necrotic and paraptotic cell death as indicated by high-level intracellular ROS, cytoplasmic vacuolization, and cell cycle arrest in the S phase. In addition, chromosomal condensations were also observed in the cells proceeding necrotic and paraptotic cell death, which was found to be related to the BAX-associated intrinsic pathway of apoptotic cell death, when Ku70 was decreased either by CBP depletion or by Ku70 depletion directly. Our results, therefore, supported the idea that CBP, Ku70, BAX, and NOX2 have formed a transcriptional network in the prevention of cell death of necrosis, paraptosis, and apoptosis in human melanoma.

scholarly journals Ca2+ overload- and ROS-associated mitochondrial dysfunction contributes to δ-tocotrienol-mediated paraptosis in melanoma cells

APOPTOSIS ◽  
2021 ◽  
Author(s):  
Michela Raimondi ◽  
Fabrizio Fontana ◽  
Monica Marzagalli ◽  
Matteo Audano ◽  
Giangiacomo Beretta ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Atp Synthesis ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Ros Generation ◽  
Therapy Outcomes ◽  
Human Melanoma Cells ◽  
Oxphos Complex

Abstract Melanoma is an aggressive tumor with still poor therapy outcomes. δ-tocotrienol (δ-TT) is a vitamin E derivative displaying potent anti-cancer properties. Previously, we demonstrated that δ-TT triggers apoptosis in human melanoma cells. Here, we investigated whether it might also activate paraptosis, a non-canonical programmed cell death. In accordance with the main paraptotic features, δ-TT was shown to promote cytoplasmic vacuolization, associated with endoplasmic reticulum/mitochondrial dilation and protein synthesis, as well as MAPK activation in A375 and BLM cell lines. Moreover, treated cells exhibited a significant reduced expression of OXPHOS complex I and a marked decrease in oxygen consumption and mitochondrial membrane potential, culminating in decreased ATP synthesis and AMPK phosphorylation. This mitochondrial dysfunction resulted in ROS overproduction, found to be responsible for paraptosis induction. Additionally, δ-TT caused Ca2+ homeostasis disruption, with endoplasmic reticulum-derived ions accumulating in mitochondria and activating the paraptotic signaling. Interestingly, by using both IP3R and VDAC inhibitors, a close cause-effect relationship between mitochondrial Ca2+ overload and ROS generation was evidenced. Collectively, these results provide novel insights into δ-TT anti-melanoma activity, highlighting its ability to induce mitochondrial dysfunction-mediated paraptosis. Graphic Abstract δ-tocotrienol induces paraptotic cell death in human melanoma cells, causing endoplasmic reticulum dilation and mitochondrial swelling. These alterations induce an impairment of mitochondrial function, ROS production and calcium overload.

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.

scholarly journals 68Ga-DOTA-GGNle-CycMSHhextargets the melanocortin-1 receptor for melanoma imaging

2018 ◽  
Vol 10 (466) ◽  
pp. eaau4445 ◽  
Author(s):  
Jianquan Yang ◽  
Jingli Xu ◽  
Rene Gonzalez ◽  
Thomas Lindner ◽  
Clemens Kratochwil ◽  
...  
Keyword(s):  
Melanoma Cells ◽  
Molecular Target ◽  
Therapeutic Agents ◽  
Human Melanoma ◽  
Emission Tomography ◽  
Melanocortin 1 Receptor ◽  
Imaging Probe ◽  
Specific Targeting ◽  
Human Melanoma Cells ◽  
Positron Emission

Melanocortin-1 receptor (MC1R) is a molecular target for melanoma imaging and therapy because of its overexpression on rodent and human melanoma cells. Here, we evaluated the MC1R targeting and specificity of68Ga-DOTA-GGNle-CycMSHhexand Cy5.5-GGNle-CycMSHhexusing murine and human melanoma cells, and murine and xenografted tumors.68Ga-DOTA-GGNle-CycMSHhexwas used first in human as an imaging probe to evaluate the possibility of radionuclide therapy in patients with advanced-stage melanoma.68Ga-DOTA-GGNle-CycMSHhexand Cy5.5-GGNle-CycMSHhexdisplayed MC1R-specific targeting properties in murine and human melanoma cells, as well as in murine melanoma and human melanoma–xenografted tumors. Both B16/F10 and M21 melanoma lesions could be easily imaged by positron emission tomography using68Ga-DOTA-GGNle-CycMSHhex. The first-in-human images of melanoma brain metastases in patients demonstrated the clinical relevance of MC1R as a molecular target for melanoma imaging, highlighting the potential of68Ga-DOTA-GGNle-CycMSHhexas an MC1R-targeting melanoma imaging probe and underscoring the need to develop MC1R-targeting therapeutic agents for treating patients with metastatic melanoma.

scholarly journals Identification and Characterization of NTB451 as a Potential Inhibitor of Necroptosis

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2884 ◽  
Author(s):  
Eun-Jung In ◽  
Yuno Lee ◽  
Sushruta Koppula ◽  
Tae-Yeon Kim ◽  
Jun-Hyuk Han ◽  
...  
Keyword(s):  
Cell Death ◽  
Md Simulation ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Direct Interaction ◽  
Inhibitory Effect ◽  
Therapeutic Implications ◽  
Pathological Conditions ◽  
Tnf Α

Necroptosis, or caspase-independent programmed cell death, is known to be involved in various pathological conditions, such as ischemia/reperfusion injury, myocardial infarction, atherosclerosis, and inflammatory bowel diseases. Although several inhibitors of necroptosis have been identified, none of them are currently in clinical use. In the present study, we identified a new compound, 4-({[5-(4-aminophenyl)-4-ethyl-4H-1,2,4-triazol-3-yl]sulfanyl}methyl)-N-(1,3-thiazol-2-yl) benzamide (NTB451), with significant inhibitory activity on the necroptosis induced by various triggers, such as tumor necrosis factor-α (TNF-α) and toll-like receptor (TLR) agonists. Mechanistic studies revealed that NTB451 inhibited phosphorylation and oligomerization of mixed lineage kinase domain like (MLKL), and this activity was linked to its inhibitory effect on the formation of the receptor interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3 complex. Small interfering RNA (siRNA)-mediated RIPK1 knockdown, drug affinity responsive target stability assay, and molecular dynamics (MD) simulation study illustrated that RIPK1 is a specific target of NTB451. Moreover, MD simulation showed a direct interaction of NTB451 and RIPK1. Further experiments to ensure that the inhibitory effect of NTB451 was restricted to necroptosis and NTB451 had no effect on nuclear factor-κB (NF-κB) activation or apoptotic cell death upon triggering with TNF-α were also performed. Considering the data obtained, our study confirmed the potential of NTB451 as a new necroptosis inhibitor, suggesting its therapeutic implications for pathological conditions induced by necroptotic cell death.

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