A synthetic channel that efficiently inserts into mammalian cell membranes and destroys cancer cells

2018 ◽  
Vol 209 ◽  
pp. 149-159 ◽  
Author(s):  
Jian-Yu Chen ◽  
Wei-Wei Haoyang ◽  
Min Zhang ◽  
Gang Wu ◽  
Zhan-Ting Li ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mammalian Cell ◽  
Mammalian Cells ◽  
Cell Membranes ◽  
Amino Groups ◽  
Positively Charged ◽  
Strong Ability

A tubular molecule with terminal positively charged amino groups that displays a strong ability to insert into the membrane of mammalian cells.

scholarly journals Graphene Oxide Composite for Selective Recognition, Capturing, Photothermal Killing of Bacteria over Mammalian Cells

Polymers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1116 ◽  
Author(s):  
Gang Ma ◽  
Junjie Qi ◽  
Qifan Cui ◽  
Xueying Bao ◽  
Dong Gao ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Mammalian Cells ◽  
Selective Recognition ◽  
Great Promise ◽  
Poly Ethylene Glycol ◽  
Amino Groups ◽  
Low Cytotoxicity ◽  
Poly Ethylene ◽  
Insight Into ◽  
Positively Charged

The multifunctional photothermal therapy (PTT) platform with the ability to selectively kill bacteria over mammalian cells has received widespread attention recently. Herein, we prepared graphene oxide-amino(polyethyleneglycol) (GO-PEG-NH2) while using the hydrophobic interaction between heptadecyl end groups of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethyleneglycol)] (DSPE-PEG-NH2) and graphene oxide (GO). Based on GO-PEG-NH2, the versatile PTT system was constructed with simultaneous selective recognition, capturing, and photothermal killing of bacteria. When the cells undergo bacterial infection, owing to the poly(ethylene glycol) (PEG) chains and positively charged amino groups, GO-PEG-NH2 can specifically recognize and capture bacteria in the presence of cells. Meanwhile, the stable photothermal performance of GO-PEG-NH2 enables the captured bacteria to be efficiently photothermally ablated upon the irradiation of 808 nm laser. Besides, the GO-PEG-NH2 is highly stable in various biological media and it exhibits low cytotoxicity, suggesting that it holds great promise for biological applications. This work provides new insight into graphene-based materials as a PTT agent for the development of new therapeutic platforms.

scholarly journals Glutathione peroxidase-1 regulates ASK1-dependent apoptosis via interaction with TRAF2 in RIPK3-negative cancer cells

2021 ◽  
Author(s):  
Sunmi Lee ◽  
Eun-Kyung Lee ◽  
Dong Hoon Kang ◽  
Jiyoung Lee ◽  
Soo Hyun Hong ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Cancer Cells ◽  
Mammalian Cells ◽  
Apoptosis Pathway ◽  
Glutathione Peroxidase 1 ◽  
Peroxidase Enzyme ◽  
Thioredoxin 1 ◽  
Sequential Activation ◽  
Induced Apoptosis

AbstractGlutathione peroxidase (GPx) is a selenocysteine-containing peroxidase enzyme that defends mammalian cells against oxidative stress, but the role of GPx signaling is poorly characterized. Here, we show that GPx type 1 (GPx1) plays a key regulatory role in the apoptosis signaling pathway. The absence of GPx1 augmented TNF-α-induced apoptosis in various RIPK3-negative cancer cells by markedly elevating the level of cytosolic H2O2, which is derived from mitochondria. At the molecular level, the absence of GPx1 led to the strengthened sequential activation of sustained JNK and caspase-8 expression. Two signaling mechanisms are involved in the GPx1-dependent regulation of the apoptosis pathway: (1) GPx1 regulates the level of cytosolic H2O2 that oxidizes the redox protein thioredoxin 1, blocking ASK1 activation, and (2) GPx1 interacts with TRAF2 and interferes with the formation of the active ASK1 complex. Inducible knockdown of GPx1 expression impaired the tumorigenic growth of MDA-MB-231 cells (>70% reduction, P = 0.0034) implanted in mice by promoting apoptosis in vivo. Overall, this study reveals the apoptosis-related signaling function of a GPx family enzyme highly conserved in aerobic organisms.

scholarly journals A Novel Nanobody Precisely Visualizes Phosphorylated Histone H2AX in Living Cancer Cells under Drug-Induced Replication Stress

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3317
Author(s):  
Eric Moeglin ◽  
Dominique Desplancq ◽  
Audrey Stoessel ◽  
Christian Massute ◽  
Jeremy Ranniger ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mammalian Cells ◽  
Chromatin Modification ◽  
Replication Stress ◽  
Living Cells ◽  
Single Step ◽  
Dna Double Strand Breaks ◽  
Drug Induced ◽  
Histone H2ax ◽  
C Terminus

Histone H2AX phosphorylated at serine 139 (γ-H2AX) is a hallmark of DNA damage, signaling the presence of DNA double-strand breaks and global replication stress in mammalian cells. While γ-H2AX can be visualized with antibodies in fixed cells, its detection in living cells was so far not possible. Here, we used immune libraries and phage display to isolate nanobodies that specifically bind to γ-H2AX. We solved the crystal structure of the most soluble nanobody in complex with the phosphopeptide corresponding to the C-terminus of γ-H2AX and show the atomic constituents behind its specificity. We engineered a bivalent version of this nanobody and show that bivalency is essential to quantitatively visualize γ-H2AX in fixed drug-treated cells. After labelling with a chemical fluorophore, we were able to detect γ-H2AX in a single-step assay with the same sensitivity as with validated antibodies. Moreover, we produced fluorescent nanobody-dTomato fusion proteins and applied a transduction strategy to visualize with precision γ-H2AX foci present in intact living cells following drug treatment. Together, this novel tool allows performing fast screenings of genotoxic drugs and enables to study the dynamics of this particular chromatin modification in individual cancer cells under a variety of conditions.

Positively charged gold nanoparticles capped with folate quaternary chitosan: Synthesis, cytotoxicity, and uptake by cancer cells

2018 ◽  
Vol 183 ◽  
pp. 140-150 ◽  
Author(s):  
Hui-ju Yen ◽  
Yen-an Young ◽  
Tsung-neng Tsai ◽  
Kuang-ming Cheng ◽  
Xin-an Chen ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Cancer Cells ◽  
Positively Charged Gold Nanoparticles ◽  
Positively Charged

scholarly journals Pathogenesis of shigella diarrhea. VII. Evidence for a cell membrane toxin receptor involving β1 {arrow} 4-linked N-acetyl-D-glucosamine oligomers

1977 ◽  
Vol 146 (2) ◽  
pp. 535-546 ◽  
Author(s):  
GT Keusch ◽  
M Jacewicz
Keyword(s):  
Cell Membrane ◽  
Cholera Toxin ◽  
Liver Cell ◽  
Hela Cells ◽  
Mammalian Cells ◽  
Cell Membranes ◽  
Proteolytic Enzymes ◽  
Cell Monolayer ◽  
Toxin Receptor ◽  
Toxin Uptake

The binding of ShigeUa dysenteriae 1 cytotoxin to HeLa cells in culture and to isolated rat liver cell membranes was studied by means of an indirect consumption assay of toxicity from the medium, or by determination of cytotoxicity to the HeLa cell monolayer. Both liver cell membranes and HeLa cells removed toxicity from the medium during incubation, in contrast to WI-38 and Y-1 mouse adrenal tumor cells, both of which neither bound nor were affected by the toxin. Uptake of toxin was directly related to concentration of membranes added, time,and temperature, and indirectly related to the ionic strength of the buffer used. The chemical nature of the membrane receptor was characterized by using three principal approaches: (a) enzymatic sensitivity; (b) competitive inhibition and (c) receptor blockade studies. The receptor was destroyed by proteolytic enzymes, phospholipases (which markedly altered the gross appearance of the membrane preparation) and by lysozyme, but not by a variety of other enzymes. Of 28 carbohydrate and glycoprotein haptens studied, including cholera toxin and ganglioside, only the chitin oligosaccharide lysozyme substrates, per N-acetylated chitotriose, chitotetraose, and chitopentaose were effective competitive inhibitors. Greatest inhibition was found with the trimer, N, N', N" triacetyl chitotriose. Of three lectins studied as possible receptor blockers, including phytohemagglutinin, concanavalin A, and wheat germ agglutinin, only the latter, which is known to possess specific binding affinity for N, N', N" triacetyl chitotriose, was able to block toxin uptake. Evidence from all three approaches indicate, therefore, existence of a glycoprotein toxin receptor on mammalian cells, with involvement of oligomeric β1{arrow}4-1inked N-acetyl glucosamine in the receptor. This receptor is clearly distinct from the G(M1) ganglioside thought to be involved in the binding of cholera toxin to the cell membrane of a variety of cell types susceptible to its action.

scholarly journals Tropism of Extracellular Vesicles and Cell-Derived Nanovesicles to Normal and Cancer Cells: New Perspectives in Tumor-Targeted Nucleic Acid Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1911
Author(s):  
Anastasiya Oshchepkova ◽  
Oleg Markov ◽  
Evgeniy Evtushenko ◽  
Alexander Chernonosov ◽  
Elena Kiseleva ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Mammalian Cells ◽  
Cytochalasin B ◽  
Drug Carrier ◽  
Membrane Vesicles ◽  
Nucleic Acid Delivery ◽  
Isolation And Purification ◽  
Cellular Origin ◽  
Efficient Uptake

The main advantage of extracellular vesicles (EVs) as a drug carrier system is their low immunogenicity and internalization by mammalian cells. EVs are often considered a cell-specific delivery system, but the production of preparative amounts of EVs for therapeutic applications is challenging due to their laborious isolation and purification procedures. Alternatively, mimetic vesicles prepared from the cellular plasma membrane can be used in the same way as natural EVs. For example, a cytoskeleton-destabilizing agent, such as cytochalasin B, allows the preparation of membrane vesicles by a series of centrifugations. Here, we prepared cytochalasin-B-inducible nanovesicles (CINVs) of various cellular origins and studied their tropism in different mammalian cells. We observed that CINVs derived from human endometrial mesenchymal stem cells exhibited an enhanced affinity to epithelial cancer cells compared to myeloid, lymphoid or neuroblastoma cancer cells. The dendritic cell-derived CINVs were taken up by all studied cell lines with a similar efficiency that differed from the behavior of DC-derived EVs. The ability of cancer cells to internalize CINVs was mainly determined by the properties of recipient cells, and the cellular origin of CINVs was less important. In addition, receptor-mediated interactions were shown to be necessary for the efficient uptake of CINVs. We found that CINVs, derived from late apoptotic/necrotic cells (aCINVs) are internalized by in myelogenous (K562) 10-fold more efficiently than CINVs, and interact much less efficiently with melanocytic (B16) or epithelial (KB-3-1) cancer cells. Finally, we found that CINVs caused a temporal and reversible drop of the rate of cell division, which restored to the level of control cells with a 24 h delay.

scholarly journals Diversity Focused Semisyntheses of Tetronate Polyether Ionophores

2019 ◽  
Author(s):  
Shaoquan Lin ◽  
Han Liu ◽  
Esben B. Svenningsen ◽  
Christine Pedersen ◽  
Peter Nørby ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Cancer Cells ◽  
Mammalian Cells ◽  
Biological Activities ◽  
Structural Diversity ◽  
Bacterial Activity ◽  
Cation Binding ◽  
Detailed Understanding ◽  
Structure Activity ◽  
Aggressive Cancer

The polyether ionophores are complex natural products capable of transporting cations across biological membranes. Many family members possess highly potent antimicrobial activity and a few selected compounds have ability to target particularly aggressive cancer cells. Despite these interesting perspectives, a detailed understanding of the cellular mode-of-action of polyether ionophores is generally lacking. In principle, broad mapping of structure-activity relationships across several biological activities could provide mechanistic insights as well as identification of lead structures but access to structural diversity within the overall class is synthetically very challenging. In this manuscript, we demonstrate that novel polyether ionophores can be constructed by recycling components of highly abundant polyethers. We provide the first examples of synthetically incorporating halogen-functionalized tetronic acids as cation-binding groups into polyether ionophores and we identify analogs with strong anti-bacterial activity and minimal effects on mammalian cells.

Mitophagy in Carcinogenesis and Tumor progression- A New paradigm with Emerging Importance

2021 ◽  
Vol 21 ◽  
Author(s):  
Suman K. Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Mammalian Cells ◽  
Mitochondrial Dynamics ◽  
Clinical Importance ◽  
Malignant Cells ◽  
Malignant Growth ◽  
New Paradigm ◽  
Pancreatic Cancer Cells

: The term Mitophagy has been newly concerned in reforming metabolic landscape inside cancerous cells in addition to interface between malignant cells as well as other major constituents of tumor microenvironment. Several profoundly interrelated systems, comprising mitochondrial dynamics and mitophagy, function in mammalian cells as vital mitochondrial regulator process, and their consequence in neoplastic development has newly illuminated clinically. In specific instance of cancer cells, mitochondrialprotected metabolic paths are revamped to meet expanded bioenergetics along with biosynthetic necessities of malignant cells in addition to deal with oxidative stress. It is an exhausting task to foresee the role that mitophagy has on malignant growth cells since it relies upon various elements like cancer variability, malignant growth phase, genetic background and harmony between cell demand and accessibility. As per condition, mitophagy may have a double role as cancer suppressor for example Atg5 (autophagy related 5) or Atg7 (autophagy related 7) or execute promoter like function for instance FUNDC1 (FUN14 domain-containing protein 1), BNIP3 (BCL2/adenovirus E1B 19-kDa-interacting protein 3), PINK1 (PTEN-instigated kinase 1) etc. Tumor suppressive function of Parkin (E3 ubiquitin ligase) is likewise distinguished in mammary gland carcinoma where obstruction of mitophagy impacts tumor progression. In pancreatic cancer cells and in hepatocellular carcinoma hypermethylation of the BNIP3, promoter occurs that prevent HIF-1 (HypoxiaInducible Factor 1) binding besides ensuing initiation of mitophagy. Since the double role mitophagy has in malignant growth relying upon various circumstances and cell varieties, a range of studies have been going on mitophagy and its role in cancer progression and development is opening up a new paradigm with immense clinical importance.

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