scholarly journals Detachment Stress Mediated Bioenergetic Switch of Malignant Melanoma Cells Into Anti-Warburg Phenotype

2021 ◽  
Author(s):  
WuChing Uen ◽  
TingTing Tseng ◽  
Ching-Po Wu ◽  
ShaoChen Lee
Keyword(s):  
Drug Sensitivity ◽  
Aerobic Glycolysis ◽  
Metastatic Tumor ◽  
Melanoma Cells ◽  
Glucose Depletion ◽  
Electron Transport Chains ◽  
Tumor Phenotype ◽  
Metastatic Process ◽  
Potential Therapeutics ◽  
A375 Cells

Abstract One of the biological features of cancer cells was their aerobic glycolysis by extensive glucose fermentation to harvest energy, so called Warburg effect. Melanoma is one of the most aggressive human cancers with poor prognosis and high mortality for its high metastatic ability. During the metastatic process, the metastatic tumor cells should survive under detachment stress. However, whether the detachment stress could affect the tumor phenotype was worthy to investigate. We had established human melanoma A375 cells under detachment stress, which mimicked circulating melanoma. It was shown the detachment stress altered melanoma cell activities, malignancy, and drug sensitivity. In this study, we found that adherent melanoma cells were more sensitive to glucose depletion. However, detachment stress reduced lactate secretion owing to the reduced MCT4 and GLUT1 expressions, the altered glycolytic and respiratory capacities, and the increased superoxide production. Detachment stress also increase the sensitivity of melanoma cells toward blockade of electron transport chains. Investigation of the change in glucose metabolism of melanoma cells under detachment stress would be critical to provide novel molecular mechanism to develop potential therapeutics

scholarly journals Apolar and polar transitions drive the conversion between amoeboid and mesenchymal shapes in melanoma cells

2015 ◽  
Vol 26 (22) ◽  
pp. 4163-4170 ◽  
Author(s):  
Sam Cooper ◽  
Amine Sadok ◽  
Vicky Bousgouni ◽  
Chris Bakal
Keyword(s):  
Quantitative Imaging ◽  
Three Dimensional ◽  
Shape Space ◽  
Melanoma Cells ◽  
Collagen Matrices ◽  
Morphological Heterogeneity ◽  
Rho Family Gtpases ◽  
Metastatic Process ◽  
Rho Family ◽  
Single Living

Melanoma cells can adopt two functionally distinct forms, amoeboid and mesenchymal, which facilitates their ability to invade and colonize diverse environments during the metastatic process. Using quantitative imaging of single living tumor cells invading three-dimensional collagen matrices, in tandem with unsupervised computational analysis, we found that melanoma cells can switch between amoeboid and mesenchymal forms via two different routes in shape space—an apolar and polar route. We show that whereas particular Rho-family GTPases are required for the morphogenesis of amoeboid and mesenchymal forms, others are required for transitions via the apolar or polar route and not amoeboid or mesenchymal morphogenesis per se. Altering the transition rates between particular routes by depleting Rho-family GTPases can change the morphological heterogeneity of cell populations. The apolar and polar routes may have evolved in order to facilitate conversion between amoeboid and mesenchymal forms, as cells are either searching for, or attracted to, particular migratory cues, respectively.

scholarly journals A Novel Fast Photothermal Therapy Using Hot Spots of Gold Nanorods for Malignant Melanoma Cells

Nanomaterials ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. 880 ◽  
Author(s):  
Yanhua Yao ◽  
Nannan Zhang ◽  
Xiao Liu ◽  
Qiaofeng Dai ◽  
Haiying Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Malignant Melanoma ◽  
Gold Nanorods ◽  
Plasmon Resonance ◽  
Photothermal Therapy ◽  
Treatment Time ◽  
High Energy ◽  
Melanoma Cells ◽  
Photothermal Effect ◽  
A375 Cells

In this paper, the plasmon resonance effects of gold nanorods was used to achieve rapid photothermal therapy for malignant melanoma cells (A375 cells). After incubation with A375 cells for 24 h, gold nanorods were taken up by the cells and gold nanorod clusters were formed naturally in the organelles of A375 cells. After analyzing the angle and space between the nanorods in clusters, a series of numerical simulations were performed and the results show that the plasmon resonance coupling between the gold nanorods can lead to a field enhancement of up to 60 times. Such high energy localization causes the temperature around the nanorods to rise rapidly and induce cell death. In this treatment, a laser as low as 9.3 mW was used to irradiate a single cell for 20 s and the cell died two h later. The cell death time can also be controlled by changing the power of laser which is focused on the cells. The advantage of this therapy is low laser treatment power, short treatment time, and small treatment range. As a result, the damage of the normal tissue by the photothermal effect can be greatly avoided.

scholarly journals The Induction of Apoptosis in A375 Malignant Melanoma Cells bySutherlandia frutescens

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Nicola B. van der Walt ◽  
Zahra Zakeri ◽  
Marianne J. Cronjé
Keyword(s):  
Malignant Melanoma ◽  
Basic Mechanism ◽  
Melanoma Cells ◽  
Caspase Activation ◽  
Nuclear Condensation ◽  
Induced Apoptosis ◽  
Apoptosis Inducing Factor ◽  
A375 Melanoma Cell Line ◽  
A375 Cells

Sutherlandia frutescensis a medicinal plant indigenous to Southern Africa and is commonly known as the “cancer bush.” This plant has traditionally been used for the treatment of various ailments, although it is best known for its claims of activity against “internal” cancers. Here we report on its effect on melanoma cells. The aim of this study was to investigate whether an extract ofS. frutescenscould induce apoptosis in the A375 melanoma cell line and to outline the basic mechanism of action.S. frutescensextract induced apoptosis in A375 cells as evidenced by morphological features of apoptosis, phosphatidylserine exposure, nuclear condensation, caspase activation, and the release of cytochromecfrom the mitochondria. Studies in the presence of a pan-caspase inhibitor allude to caspase-independent cell death, which appeared to be mediated by the apoptosis inducing factor. Taken together, the results of this study show thatS. frutescensextract is effective in inducing apoptosis in malignant melanoma cells and indicates that furtherin vivomechanistic studies may be warranted.

scholarly journals The Efficacy of Dandelion Root Extract in Inducing Apoptosis in Drug-Resistant Human Melanoma Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
S. J. Chatterjee ◽  
P. Ovadje ◽  
M. Mousa ◽  
C. Hamm ◽  
S. Pandey
Keyword(s):  
Surgical Excision ◽  
Natural Compounds ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Root Extract ◽  
Nuclear Condensation ◽  
Apoptotic Pathway ◽  
Outer Leaflet ◽  
Human Melanoma Cells ◽  
A375 Cells

Notoriously chemoresistant melanoma has become the most prevalent form of cancer for the 25–29 North American age demographic. Standard treatment after early detection involves surgical excision (recurrence is possible), and metastatic melanoma is refractory to immuno-, radio-, and most harmful chemotherapies. Various natural compounds have shown efficacy in killing different cancers, albeit not always specifically. In this study, we show that dandelion root extract (DRE) specifically and effectively induces apoptosis in human melanoma cells without inducing toxicity in noncancerous cells. Characteristic apoptotic morphology of nuclear condensation and phosphatidylserine flipping to the outer leaflet of the plasma membrane of A375 human melanoma cells was observed within 48 hours. DRE-induced apoptosis activates caspase-8 in A375 cells early on, demonstrating employment of an extrinsic apoptotic pathway to kill A375 cells. Reactive Oxygen Species (ROS) generated from DRE-treated isolated mitochondria indicates that natural compounds in DRE can also directly target mitochondria. Interestingly, the relatively resistant G361 human melanoma cell line responded to DRE when combined with the metabolism interfering antitype II diabetic drug metformin. Therefore, treatment with this common, yet potent extract of natural compounds has proven novel in specifically inducing apoptosis in chemoresistant melanoma, without toxicity to healthy cells.

scholarly journals An Orthotopic Model of Uveal Melanoma in Zebrafish Embryo: A Novel Platform for Drug Evaluation

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1873
Author(s):  
Chiara Tobia ◽  
Daniela Coltrini ◽  
Roberto Ronca ◽  
Alessandra Loda ◽  
Jessica Guerra ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Zebrafish Embryo ◽  
Drug Evaluation ◽  
Metastatic Tumor ◽  
Melanoma Cells ◽  
Response To Therapy ◽  
Neoplastic Disease ◽  
Zebrafish Embryos ◽  
Orthotopic Model

Uveal melanoma is a highly metastatic tumor, representing the most common primary intraocular malignancy in adults. Tumor cell xenografts in zebrafish embryos may provide the opportunity to study in vivo different aspects of the neoplastic disease and its response to therapy. Here, we established an orthotopic model of uveal melanoma in zebrafish by injecting highly metastatic murine B16-BL6 and B16-LS9 melanoma cells, human A375M melanoma cells, and human 92.1 uveal melanoma cells into the eye of zebrafish embryos in the proximity of the developing choroidal vasculature. Immunohistochemical and immunofluorescence analyses showed that melanoma cells proliferate during the first four days after injection and move towards the eye surface. Moreover, bioluminescence analysis of luciferase-expressing human 92.1 uveal melanoma cells allowed the quantitative assessment of the antitumor activity exerted by the canonical chemotherapeutic drugs paclitaxel, panobinostat, and everolimus after their injection into the grafted eye. Altogether, our data demonstrate that the zebrafish embryo eye is a permissive environment for the growth of invasive cutaneous and uveal melanoma cells. In addition, we have established a new luciferase-based in vivo orthotopic model that allows the quantification of human uveal melanoma cells engrafted in the zebrafish embryo eye, and which may represent a suitable tool for the screening of novel drug candidates for uveal melanoma therapy.

scholarly journals Isoliquiritigenin Induces Mitochondrial Dysfunction and Apoptosis by Inhibiting mitoNEET in a Reactive Oxygen Species-Dependent Manner in A375 Human Melanoma Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao-Yu Chen ◽  
Huan-Huan Ren ◽  
Dan Wang ◽  
Ying Chen ◽  
Chuan-Jun Qu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Protein ◽  
Reactive Oxygen ◽  
Melanoma Cells ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Mitochondrial Target ◽  
Sulfur Protein ◽  
A375 Cells

The mitochondrial protein mitoNEET is a type of iron-sulfur protein localized to the outer membrane of mitochondria and is involved in a variety of human pathologies including cystic fibrosis, diabetes, muscle atrophy, and neurodegeneration. In the current study, we found that isoliquiritigenin (ISL), one of the components of the root of Glycyrrhiza glabra L., could decrease the expression of mitoNEET in A375 melanoma cells. We also demonstrated that mitoNEET could regulate the content of reactive oxygen species (ROS), by showing that the ISL-mediated increase in the cellular ROS content could be mitigated by the mitoNEET overexpression. We also confirmed the important role of ROS in ISL-treated A375 cells. The increased apoptosis rate and the decreased mitochondrial membrane potential were mitigated by the overexpression of mitoNEET in A375 cells. These findings indicated that ISL could decrease the expression of mitoNEET, which regulated ROS content and subsequently induced mitochondrial dysfunction and apoptosis in A375 cells. Our findings also highlight mitoNEET as a promising mitochondrial target for cancer therapy.

Diminution of Proliferation, Migration, and Invasion of Melanoma Cells by Arctium Lappa L. Extracts

2020 ◽  
Vol 19 (2) ◽  
pp. 188-193
Author(s):  
Chulu Alateng ◽  
Yulei Liu ◽  
Gaowa Saren ◽  
Jun Ren
Keyword(s):  
Human Cancer ◽  
Melanoma Cells ◽  
Migration And Invasion ◽  
Arctium Lappa ◽  
Aggressive Form ◽  
Proliferation And Apoptosis ◽  
Regulatory Effects ◽  
A375 Cells ◽  
Stimulation Of

As a highly aggressive form of human cancer, melanoma is prone to metastasis, leading to 75% of all skin cancer deaths. The 5-year-survival rate of melanoma is below 20%. Therefore, new therapies for melanoma are urgently needed. Burdock (Arctium lappa L) root - known for its antitumor, antioxidant, anti-inflammatory, antiviral, neuroprotective, and endoplasmic reticulum stress regulatory effects - was evaluated for its effects on the proliferation and apoptosis of melanoma cells and its possible mechanism. The results show suppression of the proliferation and stimulation of apoptosis of A375 cells in vitro. Additionally, it suppressed the PI3K/AKT pathway in A375 cells. These data suggest burdock (A. lappa L) root preparation as a promising drug for the treatment of melanoma.

scholarly journals RKIP Regulates Differentiation-Related Features in Melanocytic Cells

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1451 ◽  
Author(s):  
Cristina Penas ◽  
Aintzane Apraiz ◽  
Iraia Muñoa ◽  
Yoana Arroyo-Berdugo ◽  
Javier Rasero ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Early Stage ◽  
Melanoma Cells ◽  
Cellular Motility ◽  
Protein Levels ◽  
Raf Kinase ◽  
Raf Kinase Inhibitor Protein ◽  
Tumor Phenotype ◽  
Migration Capacity

Raf Kinase Inhibitor Protein (RKIP) has been extensively reported as an inhibitor of key signaling pathways involved in the aggressive tumor phenotype and shows decreased expression in several types of cancers. However, little is known about RKIP in melanoma or regarding its function in normal cells. We examined the role of RKIP in both primary melanocytes and malignant melanoma cells and evaluated its diagnostic and prognostic value. IHC analysis revealed a significantly higher expression of RKIP in nevi compared with early-stage (stage I–II, AJCC 8th) melanoma biopsies. Proliferation, wound healing, and collagen-coated transwell assays uncovered the implication of RKIP on the motility but not on the proliferative capacity of melanoma cells as RKIP protein levels were inversely correlated with the migration capacity of both primary and metastatic melanoma cells but did not alter other parameters. As shown by RNA sequencing, endogenous RKIP knockdown in primary melanocytes triggered the deregulation of cellular differentiation-related processes, including genes (i.e., ZEB1, THY-1) closely related to the EMT. Interestingly, NANOG was identified as a putative transcriptional regulator of many of the deregulated genes, and RKIP was able to decrease the activation of the NANOG promoter. As a whole, our data support the utility of RKIP as a diagnostic marker for early-stage melanomas. In addition, these findings indicate its participation in the maintenance of a differentiated state of melanocytic cells by modulating genes intimately linked to the cellular motility and explain the progressive decrease of RKIP often described in tumors.

Sign in / Sign up

Export Citation Format

Share Document