Combination Small Molecule MEK and PI3K Inhibition Enhances Uveal Melanoma Cell Death in a Mutant GNAQ- and GNA11-Dependent Manner.
AuthorsKhalili JS, Yu X, Wang J, Hayes BC, Davies MA, Lizee G, Esmaeli B, Woodman SE,
JournalClin Cancer Res
PubMed ID22733540
Activating Q209L/P mutations in GNAQ or GNA11 (GNAQ/11) are present in approximately 80% of uveal melanomas. Mutant GNAQ/11 are not currently therapeutically targetable. Inhibiting key down-stream effectors of GNAQ/11 represents a rational therapeutic approach for uveal melanomas that harbor these mutations. The mitogen-activated protein/extracellular signal-regulated kinase/mitogen-activated protein kinase (MEK/MAPK) and ... More
AuthorsMetkar SS, Wang B, Catalan E, Anderluh G, Gilbert RJ, Pardo J, Froelich CJ,
JournalPLoS One
PubMed ID21931672
'The cytotoxic cell granule secretory pathway is essential for host defense. This pathway is fundamentally a form of intracellular protein delivery where granule proteases (granzymes) from cytotoxic lymphocytes are thought to diffuse through barrel stave pores generated in the plasma membrane of the target cell by the pore forming protein ... More
Membrane sialidase NEU3 is highly expressed in human melanoma cells promoting cell growth with minimal changes in the composition of gangliosides.
AuthorsMiyata M, Kambe M, Tajima O, Moriya S, Sawaki H, Hotta H, Kondo Y, Narimatsu H, Miyagi T, Furukawa K, Furukawa K,
JournalCancer Sci
PubMed ID21895867
'NEU3 is a membrane sialidase specific for gangliosides. Its increased expression and implication in some cancers have been reported. Here, we analyzed NEU3 expression in malignant melanoma cell lines and its roles in the cancer phenotypes. Quantitative RT-PCR revealed that high levels of the NEU3 gene were expressed at almost ... More
Pardaxin, an Antimicrobial Peptide, Triggers Caspase-Dependent and ROS-Mediated Apoptosis in HT-1080 Cells.
AuthorsHuang TC, Lee JF, Chen JY,
JournalMar Drugs
PubMed ID22073006
Pardaxin is an antimicrobial peptide (AMP) that was first isolated from secretions of the Red Sea Moses sole. The role of pardaxin in inducing apoptosis for preventing cancer has not yet been investigated. In the present study, we examined the antitumor activity of pardaxin against human fibrosarcoma HT-1080 cells; pardaxin ... More
Development of a highly sensitive in vitro endothelial cell toxicity assay for evaluating ricin toxin A chain-based vaccines or therapeutics.
AuthorsMachesky NJ, Rusnak JM, Moore EH, Dorsey CB, Ward LA
JournalToxicon
PubMed ID31207351
'The ricin toxin A chain (RTA) is responsible for ricin intoxication due to inhibition of protein synthesis. RTA is also known to cause endothelial toxicity [via a 3 amino acid sequence (x)D(y) motif that acts as a natural disintegrin] resulting in vascular leak syndrome (VLS) in humans. An in vitro ... More
Apoptosis generates mechanical forces that close the lens vesicle in the chick embryo.
AuthorsOltean A, Taber LA
JournalPhys Biol
PubMed ID28914615
'During the initial stages of eye development, optic vesicles grow laterally outward from both sides of the forebrain and come into contact with the surrounding surface ectoderm (SE). Within the region of contact, these layers then thicken locally to create placodes and invaginate to form the optic cup (primitive retina) ... More
High-Content Monitoring of Drug Effects in a 3D Spheroid Model.
'A recent decline in the discovery of novel medications challenges the widespread use of 2D monolayer cell assays in the drug discovery process. As a result, the need for more appropriate cellular models of human physiology and disease has renewed the interest in spheroid 3D culture as a pertinent model ... More
Cell swelling, softening and invasion in a three-dimensional breast cancer model.
Authors
JournalNat Phys
PubMed ID32905405
USP7 small-molecule inhibitors interfere with ubiquitin binding.
Authors
JournalNature
PubMed ID29045385
TOX is a critical regulator of tumour-specific T cell differentiation.
Authors
JournalNature
PubMed ID31207604
Suppression of MEHMO Syndrome Mutation in eIF2 by Small Molecule ISRIB.
Authors
JournalMol Cell
PubMed ID31836389
Ribosome Collisions Trigger General Stress Responses to Regulate Cell Fate.
Authors
JournalCell
PubMed ID32610081
Metabolic Reprograming via Deletion of CISH in Human iPSC-Derived NK Cells Promotes In Vivo Persistence and Enhances Anti-tumor Activity.
Authors
JournalCell Stem Cell
PubMed ID32531207
COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses.
Authors
JournalImmunity
PubMed ID33567252
Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis.
Authors
JournalNat Commun
PubMed ID28589926
Fabrication of Smart Tantalum Carbide MXene Quantum Dots with Intrinsic Immunomodulatory Properties for Treatment of Allograft Vasculopathy.
Authors
JournalAdv Funct Mater
PubMed ID35153642
A Rapid Induction Mechanism for Lin28a in Trophic Responses.
Authors
JournalMol Cell
PubMed ID28132840
High-Throughput and High-Content Micronucleus Assay in CHO-K1 Cells.
AuthorsShahane SA, Nishihara K, Xia M
JournalMethods Mol Biol
PubMed ID27518626
Visualization of micronuclei induction by chemicals and drugs enables measurement of possible compound genotoxicity. A loss of entire chromosome or a fragment of chromosome can lead to formation of micronuclei (MNi). The in vitro micronucleus assay can be conducted using nuclear dyes with high-content imaging platforms. This chapter describes the ... More
Endometrial androgen signaling and decidualization regulate trophoblast expansion and invasion in co-culture: A time-lapse study.
AuthorsWongwananuruk T, Sato T, Kajihara T, Matsumoto S, Akita M, Tamura K, Brosens JJ, Ishihara O
JournalPlacenta
PubMed ID27780540
To elucidate whether trophoblast expansion and invasion are modulated by androgen signaling in an in vitro co-culture model system with decidualizing endometrial stromal cells (ESCs).
A multiscale fluidic device for the study of dendrite-mediated cell to cell communication.
AuthorsMcCutcheon S, Majeska R, Schaffler M, Vazquez M
JournalBiomed Microdevices
PubMed ID28791515
Many cell types communicate by means of dendritic extensions via a multi-tiered set of geometric and chemical cues. Until recently, mimicking the compartmentalized in vivo cellular environment of dendrite-expressing cells such as osteocytes and motor neurons in a spatially and temporally controllable manner was limited by the challenges of in ... More
Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells.
AuthorsMármol I, Virumbrales-Muñoz M, Quero J, Sánchez-de-Diego C, Fernández L, Ochoa I, Cerrada E, Yoldi MJR
JournalJ Inorg Biochem
PubMed ID28892675
Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, ... More
Evaluation of the molecular mechanisms associated with cytotoxicity and inflammation after pulmonary exposure to different metal-rich welding particles.
AuthorsShoeb M, Kodali V, Farris B, Bishop LM, Meighan T, Salmen R, Eye T, Roberts JR, Zeidler-Erdely P, Erdely A, Antonini JM
JournalNanotoxicology
PubMed ID28660804
Welding generates a complex aerosol of incidental nanoparticles and cytotoxic metals, such as chromium (Cr), manganese (Mn), nickel (Ni), and iron (Fe). The goal was to use both in vivo and in vitro methodologies to determine the mechanisms by which different welding fumes may damage the lungs. Sprague-Dawley rats were ... More
Huntingtin Inclusions Trigger Cellular Quiescence, Deactivate Apoptosis, and Lead to Delayed Necrosis.
Competing models exist in the literature for the relationship between mutant Huntingtin exon 1 (Httex1) inclusion formation and toxicity. In one, inclusions are adaptive by sequestering the proteotoxicity of soluble Httex1. In the other, inclusions compromise cellular activity as a result of proteome co-aggregation. Using a biosensor of Httex1 conformation ... More
Mechanistic insights into selective killing of OXPHOS-dependent cancer cells by arctigenin.
AuthorsBrecht K, Riebel V, Couttet P, Paech F, Wolf A, Chibout SD, Pognan F, Krähenbühl S, Uteng M
JournalToxicol In Vitro
PubMed ID27923774
Arctigenin has previously been identified as a potential anti-tumor treatment for advanced pancreatic cancer. However, the mechanism of how arctigenin kills cancer cells is not fully understood. In the present work we studied the mechanism of toxicity by arctigenin in the human pancreatic cell line, Panc-1, with special emphasis on ... More
Autophagy Inhibition Mediates Apoptosis Sensitization in Cancer Therapy by Relieving FOXO3a Turnover.
AuthorsFitzwalter BE, Towers CG, Sullivan KD, Andrysik Z, Hoh M, Ludwig M, O'Prey J, Ryan KM, Espinosa JM, Morgan MJ, Thorburn A
JournalDev Cell
PubMed ID29533771
Macroautophagy (autophagy) is intimately linked with cell death and allows cells to evade apoptosis. This has prompted clinical trials to combine autophagy inhibitors with other drugs with the aim of increasing the likelihood of cancer cells dying. However, the molecular basis for such effects is unknown. Here, we describe a ... More
Methamphetamine Induces Apoptosis of Microglia via the Intrinsic Mitochondrial-Dependent Pathway.
AuthorsSharikova AV, Quaye E, Park JY, Maloney MC, Desta H, Thiyagarajan R, Seldeen KL, Parikh NU, Sandhu P, Khmaladze A, Troen BR, Schwartz SA, Mahajan SD
JournalJ Neuroimmune Pharmacol
PubMed ID29644532
Methamphetamine (METH) is a drug of abuse, the acute and chronic use of which induces neurotoxic responses in the human brain, ultimately leading to neurocognitive disorders. Our goals were to understand the impact of METH on microglial mitochondrial respiration and to determine whether METH induces the activation of the mitochondrial-dependent ... More
Liposomal encapsulation of silver nanoparticles enhances cytotoxicity and causes induction of reactive oxygen species-independent apoptosis.
AuthorsYusuf A, Brophy A, Gorey B, Casey A
JournalJ Appl Toxicol
PubMed ID29181855
Silver nanoparticles (AgNP) are one of the most widely investigated metallic NPs due to their promising antibacterial activities. In recent years, AgNP research has shifted beyond antimicrobial use to potential applications in the medical arena. This shift coupled with the extensive commercial applications of AgNP will further increase human exposure ... More
Alpinoid c analog inhibits angiogenesis and induces apoptosis in COLO205?cell line.
AuthorsVelatooru LR, Vakamullu S, Penugurti V, S PR
JournalChem Biol Interact
PubMed ID31071337
Diarylheptanoids display an array of biological and pharmacological properties. We previously reported the synthesis of a diarylheptanoid Alpinoid c and a series of its derivatives, evaluated their cytotoxicity against various human cancer cells. We found some of these derivatives were significantly more potent than Alpinoid c in preventing the proliferation ... More
G protein-coupled estrogen receptor activates cell type-specific signaling pathways in cortical cultures: relevance to the selective loss of astrocytes.
AuthorsRoque C, Mendes-Oliveira J, Baltazar G
JournalJ Neurochem
PubMed ID30570746
Selective activation of the G protein-coupled estrogen receptor has been proposed to avoid some of the side effects elicited by the activation of classical estrogen receptors a and ß. Although its contribution to neuroprotection triggered by estradiol in brain disorders has been explored, the results regarding ischemic stroke are contradictory, ... More
Ci-hox12 tail gradient precedes and participates in the control of the apoptotic-dependent tail regression during Ciona larva metamorphosis.
AuthorsKrasovec G, Robine K, Quéinnec E, Karaiskou A, Chambon JP
JournalDev Biol
PubMed ID30819533
At the onset of the Ciona intestinalis metamorphosis, the first event is tail regression characterized, by a contraction, an apoptotic wave and Primordial Germ Cells (PGC) movement. All these cell behaviors originate from the posterior tail tip and progress to the anterior. Interestingly, earlier in Ciona development, the antero-posterior (A/P) ... More
Paraoxonase 2 protects against acute myocardial ischemia-reperfusion injury by modulating mitochondrial function and oxidative stress via the PI3K/Akt/GSK-3ß RISK pathway.
AuthorsSulaiman D, Li J, Devarajan A, Cunningham CM, Li M, Fishbein GA, Fogelman AM, Eghbali M, Reddy ST
JournalJ Mol Cell Cardiol
PubMed ID30802459
To investigate the novel role of Paraoxonase 2 (PON2) in modulating acute myocardial ischemia-reperfusion injury (IRI).
FTY720 induces non-canonical phosphatidylserine externalization and cell death in acute myeloid leukemia.
AuthorsYoung MM, Bui V, Chen C, Wang HG
JournalCell Death Dis
PubMed ID31699964
FTY720 (fingolimod) is a FDA-approved sphingosine analog that is phosphorylated in vivo to modulate sphingosine-1-phosphate receptor (S1PR) signaling for immunosuppression in patients with refractory multiple sclerosis. FTY720 also exhibits promising anticancer efficacy in several preclinical models. While FTY720-induced cytotoxicity is not due to S1PR signaling, the mechanism remains unclear and ... More
Rosiglitazone in the thawing medium improves mitochondrial function in stallion spermatozoa through regulating Akt phosphorylation and reduction of caspase 3.
AuthorsOrtiz-Rodriguez JM, Balao da Silva C, Masot J, Redondo E, Gazquez A, Tapia JA, Gil C, Ortega-Ferrusola C, Peña FJ
JournalPLoS One
PubMed ID31276504
The population of stallion spermatozoa that survive thawing experience compromised mitochondrial functionality and accelerated senescence, among other changes. It is known that stallion spermatozoa show very active oxidative phosphorylation that may accelerate sperm senescence through increased production of reactive oxygen species. Rosiglitazone has been proven to enhance the glycolytic capability ... More
Apoptotic Osteocytes Induce RANKL Production in Bystanders via Purinergic Signaling and Activation of Pannexin Channels.
AuthorsMcCutcheon S, Majeska RJ, Spray DC, Schaffler MB, Vazquez M
JournalJ Bone Miner Res
PubMed ID31910292
Localized apoptosis of osteocytes, the tissue-resident cells within bone, occurs with fatigue microdamage and activates bone resorption. Osteoclasts appear to target and remove dying osteocytes, resorbing damaged bone matrix as well. Osteocyte apoptosis similarly activates bone resorption with estrogen loss and in disuse. Apoptotic osteocytes trigger viable neighbor (ie, bystander) ... More
Secretion of Acid Sphingomyelinase and Ceramide by Endothelial Cells Contributes to Radiation-Induced Intestinal Toxicity.
AuthorsLeonetti D, Estéphan H, Ripoche N, Dubois N, Aguesse A, Gouard S, Brossard L, Chiavassa S, Corre I, Pecqueur C, Neunlist M, Hadchity E, Gaugler MH, Mahé MM, Paris F
JournalCancer Res
PubMed ID32291318
Ceramide-induced endothelial cell apoptosis boosts intestinal stem cell radiosensitivity. However, the molecular connection between these two cellular compartments has not been clearly elucidated. Here we report that ceramide and its related enzyme acid sphingomyelinase (ASM) are secreted by irradiated endothelial cells and act as bystander factors to enhance the radiotoxicity ... More