scholarly journals CYTOTOXIC PROPERTIES OF NANOSTRUCTURES BASED ON ALUMINUM OXIDE AND HYDROXIDE PHASES IN RELATION TO TUMOR CELLS

2021 ◽  
Vol 20 (4) ◽  
pp. 73-83
Author(s):  
A. S. Lozhkomoev ◽  
O. V. Bakina ◽  
S. O. Kazantsev ◽  
L. Yu. Ivanova ◽  
A. V. Avgustinovich ◽  
...  
Keyword(s):  
Phase Composition ◽  
Antitumor Activity ◽  
Tumor Cell ◽  
Cell Viability ◽  
Tumor Cells ◽  
Tumor Therapy ◽  
Nitrogen Atmosphere ◽  
Acid Base ◽  
Cell Microenvironment ◽  
Base Properties

Background. Currently, the use of nanoparticles and nanostructures as components of tumor therapy is the subject of numerous scientific articles. To change the parameters of cell microenvironment in presence of nanoparticles and nanostructures is a promising approach to reducing the tumor cell viability. Aluminum hydroxides and oxides have a number of advantages over other particles due to their porous surface, low toxicity, and thermal stability.The purpose of the study was to investigate the influence of the acid-base properties of aluminum hydroxide structures with different phase composition on the tumor cell viability (Hela, mda, pymt, a549, B16F10).Material and methods. Aln/al nanoparticles were used as a precursor for obtaining structures with various phase compositions. The anoparticles were produced by electric explosion of an aluminum wire in a nitrogen atmosphere. Such nanoparticles interact with water at 60 °Ϲ, resulting in formation of porous nanostructures. They are agglomerates of nanosheets with a planar size of up to 200 nm and a thickness of 5 nm. The phase composition of the structures was varied by the calcination temperature. A change in the phase composition of nanostructures led to a change in the acid-base properties of their surface. To estimate the number of acidic and basic centers on the surface of nanostructures, the adsorption of Hammett indicators was used. The amount of adsorbed dyes was determined spectrophotometrically.Results. It was found that the differences in the acid-base characteristics of the surface of the nanostructures led to a change in their antitumor activity. Γ-al2o3 had 6.5 times more basic centers than acidic ones, which determined its ability to exhibit more pronounced antacid properties, i.e. Longer to neutralize protons secreted by tumor cells. This sample had the highest antitumor activity against all tested cell lines.Conclusion. The antitumor activity of synthesized structures was found to be related not only to an increase in the ph of the cell microenvironment, but also to the ability to maintain the alkalinity of the microenvironment for a longer time due to the adsorption of protons released by tumor cells.

scholarly journals RGD4C peptide mediates anti-p21Ras scFv entry into tumor cells and produces an inhibitory effect on the human colon cancer cell line SW480

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chen-Chen Huang ◽  
Fang-Rui Liu ◽  
Qiang Feng ◽  
Xin-Yan Pan ◽  
Shu-Ling Song ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Membrane ◽  
Fusion Protein ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Fusion Proteins ◽  
Inhibitory Effect ◽  
Endosomal Escape ◽  
Antitumor Effects ◽  
Sw480 Cells

Abstract Background We prepared an anti-p21Ras scFv which could specifically bind with mutant and wild-type p21Ras. However, it cannot penetrate the cell membrane, which prevents it from binding to p21Ras in the cytoplasm. Here, the RGD4C peptide was used to mediate the scFv penetration into tumor cells and produce antitumor effects. Methods RGD4C-EGFP and RGD4C-p21Ras-scFv recombinant expression plasmids were constructed to express fusion proteins in E. coli, then the fusion proteins were purified with HisPur Ni-NTA. RGD4C-EGFP was used as reporter to test the factors affecting RGD4C penetration into tumor cell. The immunoreactivity of RGD4C-p21Ras-scFv toward p21Ras was identified by ELISA and western blotting. The ability of RGD4C-p21Ras-scFv to penetrate SW480 cells and colocalization with Ras protein was detected by immunocytochemistry and immunofluorescence. The antitumor activity of the RGD4C-p21Ras-scFv was assessed with the MTT, TUNEL, colony formation and cell migration assays. Chloroquine (CQ) was used an endosomal escape enhancing agent to enhance endosomal escape of RGD4C-scFv. Results RGD4C-p21Ras-scFv fusion protein were successfully expressed and purified. We found that the RGD4C fusion protein could penetrate into tumor cells, but the tumor cell entry of was time and concentration dependent. Endocytosis inhibitors and a low temperature inhibited RGD4C fusion protein endocytosis into cells. The change of the cell membrane potential did not affect penetrability. RGD4C-p21Ras-scFv could penetrate SW480 cells, effectively inhibit the growth, proliferation and migration of SW480 cells and promote this cells apoptosis. In addition, chloroquine (CQ) could increase endosomal escape and improve antitumor activity of RGD4C-scFv in SW480 cells. Conclusion The RGD4C peptide can mediate anti-p21Ras scFv entry into SW480 cells and produce an inhibitory effect, which indicates that RGD4C-p21Ras-scFv may be a potential therapeutic antibody for the treatment of ras-driven cancers.

Macrophage Antitumor Activity Induced by the Antigenic Lymphoma L5178Y/DTIC Subline

1982 ◽  
Vol 68 (5) ◽  
pp. 365-371 ◽  
Author(s):  
Ornella Marelli ◽  
Alberto Mantovani ◽  
Paola Franco ◽  
Angelo Nicotin
Keyword(s):  
Antitumor Activity ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Peritoneal Macrophages ◽  
Leukemic Cells ◽  
Target Cells ◽  
Tumor Target ◽  
Growth Inhibitory

Murine leukemic cells, after in vivo treatment with antineoplastic drugs, have been shown to express new antigenic specificities that were not detectable on parental cells and that were heritable after the withdrawal of drug treatment. A study was conducted of macrophage antitumor activity triggered by LY/DTIC cells, a subline of LY murine lymphoma, antigenically altered by the drug DTIC. In vitro non-specific inhibition of tumor cell growth was exhibited by spleen and peritoneal macrophages from mice previously challenged with viable LY/DTIC. Peritoneal macrophages from LY/DTIC immune animals showed moderate, although significant lytic activity against unrelated tumor target cells. Supernatants from mixed lymphocyte-tumor cell cultures, in which LY/DTIC immune lymphocytes and LY/DTIC tumor cells had been cultured, rendered normal macrophages non-specifically growth inhibitory for tumor cells.

scholarly journals Transdifferentiation mediated tumor suppression by the endoplasmic reticulum stress sensor IRE-1 in C. elegans

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Mor Levi-Ferber ◽  
Hai Gian ◽  
Reut Dudkevich ◽  
Sivan Henis-Korenblit
Keyword(s):  
Tumor Cell ◽  
Er Stress ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Tumor Therapy ◽  
Tumor Model ◽  
Apoptosis Resistance ◽  
Stress Sensor ◽  
C Elegans ◽  
Cell Transdifferentiation

Deciphering effective ways to suppress tumor progression and to overcome acquired apoptosis resistance of tumor cells are major challenges in the tumor therapy field. We propose a new concept by which tumor progression can be suppressed by manipulating tumor cell identity. In this study, we examined the effect of ER stress on apoptosis resistant tumorous cells in a Caenorhabditis elegans germline tumor model. We discovered that ER stress suppressed the progression of the lethal germline tumor by activating the ER stress sensor IRE-1. This suppression was associated with the induction of germ cell transdifferentiation into ectopic somatic cells. Strikingly, transdifferentiation of the tumorous germ cells restored their ability to execute apoptosis and enabled their subsequent removal from the gonad. Our results indicate that tumor cell transdifferentiation has the potential to combat cancer and overcome the escape of tumor cells from the cell death machinery.

Anti-Myeloma Effects of the Janus Kinase 2 (JAK2) Inhibitor SAR503 Alone and in Combination Treatment

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4986-4986
Author(s):  
Haiming Chen ◽  
Mingjie Li ◽  
Jennifer Li ◽  
Kevin Delijani ◽  
Danielle Rauch ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Cell Viability ◽  
Tumor Cells ◽  
Cell Lines ◽  
Drug Exposure ◽  
Single Agent ◽  
Janus Kinase ◽  
Gm Csf ◽  
Jak2 Inhibitor

Abstract Abstract 4986 Background: Janus kinase 2 (JAK2) is a cytoplasmic tyrosine kinase that carries out a series of cascading signals via signal transducer and activator of transcription (STAT)s, mitogen-activated protein kinase (MAPK), and phosphorylation of PI3K. Activation of the JAK2 pathway plays an important role in both normal and malignant hematopoiesis. The JAK pathway ha been shown to play a key role in multiple myeloma (MM). JAK2 has been specifically implicated in signaling by members of the type II cytokine receptor family (interferon [IFN] receptor), GM-CSF receptor (IL-3R, IL-5R, and GM-CSF-R), gp130 receptor family interleukin-6 (IL-6R) and single chain receptors (Epo-R, Tpo-R, GH-R, and PRL-R). IFN-α inhibits MM cell proliferation in association with cell cycle arrest at G1 and limits the clonogenic growth of both MM cell lines and primary MM patient specimens. SAR503 (Sanofi-Aventis) is a potent, highly selective JAK2 inhibitor. Thus, we evaluated the anti-MM effects of SAR503 as a single agent and in combination with other anti-MM drugs and evaluated gene and protein expression in MM cells exposed to these drugs. Experiment design: The MM cell lines RPMI8226, U266, and MM1s were cultured in RPMI1640 with standard nutrition supplements. Bone marrow aspirates were obtained from MM patients following informed consent. Bone marrow mononuclear cells (BMMCs) were isolated by using density-gradient centrifugation with Histopaque-1077 (Sigma, St Louis). Cells were plated in 96 well plates at a concentration of 6 × 104 cells/100 ml/well, and incubated for 24 hours prior to drug treatment, after which time the drugs were added in replicates of six for 48 hours. BMMCs were incubated in the presence of media, SAR503, doxorubicin, melphalan, dexamethasone, bortezomib, or IFN-α alone or the combination of SAR503 with one of these anti-MM agents. Following the 48-hour drug incubation, cell viability was assessed utilizing the cell proliferation MTS assay. For gene expression studies, total RNA was isolated MM tumor cells with or without drug exposure. RNA was reverse-transcribed into cDNA and amplified using the Thermo-Script RT-PCR System and PCR performed again using the GeneAmp PCR System 9700. Protein phosphorylation of MM tumor cells with or without drug exposure was determined with Western blot analysis. Results: SAR503 alone inhibited MM tumor cell proliferation in a concentration-dependent fashion. The 50% growth inhibition (IC50) of cells from MM cell lines at 48 hours varied (IC50: RPMI8226 1mM; U266 0. 5mM; MM1s 10mM). IC50 of primary MM tumor cells treated with SAR503 ranged from approximately 5 to 10mM in different patients. Notably, the combination of SAR503 and either doxorubicin or melphalan showed markedly reduced cell viability compared to either drug alone in all three MM cell lines and primary tumor cells from MM patients. Since this effect may have resulted from decreased cell proliferation due to inhibition of the JAK2 pathway and cell cycle arrest or increased cell death, we further determined cell apoptosis of MM tumor cells treated with SAR503 alone by using flow cytometric analysis to detect Annexin V and propidium iodide (PI) staining. Our data showed SAR503 increased MM tumor cell apoptosis in a concentration-dependent fashion. The combination of SAR503 and dexamethasone or bortezomib only slightly reduced tumor cell viability in both MM cell lines and primary MM tumor cells more than single agent treatment, and the combination of SAR503 with IFN-α did not enhance the anti-MM effects compared to single drug treatment. Notably, RT-PCR results showed marked decreases in both AKT1 and mTOR gene expression in MM tumor cells treated with SAR503. Conclusion: The combination of the JAK2 inhibitor SAR503 with doxorubicin or melphalan markedly reduces MM tumor cell viability more than single agent treatment. The results from these studies suggest that enhanced anti-MM activity may be observed when SAR503 is combined with conventional treatment for MM. We are currently evaluating the anti-MM effects of SAR503 in these combination treatments in vivo using our MM xenograft models. Disclosures: Berenson: Onyx: Consultancy, Honoraria, Speakers Bureau.

Antiproliferative and Antitumor Activity of the 2-Cyanoaziridine Compound Imexon on Tumor Cell Lines and Fresh Tumor Cells In Vitro

1992 ◽  
Vol 84 (16) ◽  
pp. 1238-1244 ◽  
Author(s):  
E. M. Hersh ◽  
C. R. Gschwind ◽  
C. W. Taylor ◽  
R. T. Dorr ◽  
R. Taetle ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Tumor Cell Lines

scholarly journals Evaluation of the PTEN and circRNA-CDR1as Gene Expression Changes in Gastric Cancer and Normal Cell Lines Following the Exposure to Weak and Moderate 50 Hz Electromagnetic

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Fereshteh Mansoury ◽  
Nahid Babaei ◽  
Soheila Abdi ◽  
Maliheh Entezari ◽  
Abbas Doosti
Keyword(s):  
Gastric Cancer ◽  
Electromagnetic Field ◽  
Cell Viability ◽  
Real Time ◽  
Tumor Cells ◽  
Cell Lines ◽  
Electromagnetic Fields ◽  
Tumor Therapy ◽  
Pten Gene ◽  
Tensin Homolog

Background: Attention to the electromagnetic exposure as a targeted tumor therapy has been recently increasing. Objectives: The aim of the current study was to investigate the effect of continuous and discontinuous electromagnetic fields on cell viability as well as phosphatase and tensin homolog (PTEN) and circular (circ)-RNA CDR1as genes expression in the normal and gastric cancer (GC) cell lines. Methods: After preparing gastric cancer cell lines (AGS) and normal cells (HU02 line), they were exposed to magnetic flux densities of 0.25, 0.5, 1, and 2 mT continuously and discontinuously (1h on/1h off) for 18 hours. The 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cell viability. In addition, after designing the primers, the expression of the PTEN and circ-CDR1as genes was studied using the real-time polymerase chain reaction (real-time-PCR) technique. The results were analyzed using SPSS software version 25. Results: The exposed normal and tumor cells to discontinuous electromagnetic fields resulted in increasing of cell survival rate in both normal and tumor cells. In contrast, the exposure of continuous electromagnetic field showed no effect on the viability of the normal and tumor cells at intensities of 0.25, 0.5, and 1 mT. The electromagnetic field showed a significant effect on the expression of the circ-CDR1as gene and this effect depended on the intensity of the electromagnetic field used and the cell type. We have found that the activity of PTEN gene in the normal and tumor cells increased and decreased with increasing intensity of discontinuous electromagnetic field, respectively. Conclusions: In general, the effect of electromagnetic field on gastric cancer seems to depend on the kind of exposure as well as an extent of intensity and can be used for cancer therapeutic purposes. However, more research is needed on this subject.

Using a hybrid radioenhancer to realize tumor cell-targeted treatment for osteosarcoma: an in vitro study

2020 ◽  
Vol 27 ◽  
Author(s):  
Fu-I Tung ◽  
Li-Chin Chen ◽  
Yu-Chi Wang ◽  
Ming-Hong Chen ◽  
Pei-Wei Shueng ◽  
...  
Keyword(s):  
Western Blot ◽  
Tumor Cell ◽  
Cell Viability ◽  
Tumor Cells ◽  
Clonogenic Assay ◽  
Normal Cells ◽  
Targeted Radiotherapy ◽  
In Vitro Investigation ◽  
Dose Radiation

: Osteosarcoma is insensitive to radiation. High-dose radiation is often used as a treatment, but causes side effects in patients. Hence, it is important to develop tumor cell-targeted radiotherapy that could improve radiotherapy efficiency on tumor cells and reduce the toxic effect on normal cells during radiation treatment. In this study, we developed an innovative method for treating osteosarcoma by using a novel radiation-enhancer (i.e., carboxymethyl-hexanoyl chitosan-coated selfassembled Au@Fe3O4 nanoparticles; CSAF NPs). CSAF NPs were employed together with 5-aminolevulinic acid (5-ALA) to achieve tumor cell-targeted radiotherapy. In this study, osteosarcoma cells (MG63) and normal cells (MC3T3-E1) were used for an in vitro investigation, in which a reactive oxygen species (ROS) assay, cell viability assay, clonogenic assay, and western blot were used to confirm the treatment efficiency. The ROS assay showed that the combination of CSAF NPs and 5-ALA enhanced radiation-induced ROS production in tumor cells (MG63); however, this was not observed in normal cells (MC3T3-E1). The cell viability ratio of normal cells to tumor cells after treatment with CSAF NPs and 5-ALA reached 2.79. Moreover, the clonogenic assay showed that the radiosensitivity of MG63 cells was increased by the combination use of CSAF NPs and 5-ALA. This was supported by performing a western blot that confirmed expression of cytochrome c (a marker of cell mitochondria damage) and caspase-3 (a marker of cell apoptosis). The results provide an essential basis for developing tumor-cell targeted radiotherapy by means of low-dose radiation.

Essential experimental steps and estimates of renal carcinoma initiating cells.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 11127-11127
Author(s):  
Craig Gedye ◽  
Danylo Sirskyj ◽  
Nazleen Carol Lobo ◽  
Ella Hyatt ◽  
Andrew Evans ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Viability ◽  
Tumor Cells ◽  
Cell Lines ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Rock Inhibitor ◽  
Cell Renal Cell Carcinoma ◽  
Cell Potential

11127 Background: Rare cancer stem cells (CSC), proposed to be solely responsible for tumor propagation and re-initiation, are functionally identified as tumor-initiating cells (TIC) from ex vivo tumors using xenotransplantation and clonogenic limiting dilution assays (LDA). TIC have not previously been described from ex vivohuman clear cell renal cell carcinoma (ccRCC). Methods: Primary human ccRCC samples (n=120) from patients undergoing nephrectomy were processed and implanted as subcapsular fragments or cell suspension injection LDAs with Matrigel in NOD/SCID/IL2Rγ-/- (NSG) mice, and observed for at least 6 months. In vitro clonogenic LDAs assays were performed from primary cell suspensions and ccRCC cell lines. LDAs were supplemented with human stromal cells and proteins, and the Y-26732 ROCK inhibitor. Multiparametric flow cytometry and immunofluorescence were used to investigate tumor heterogeneity and cell viability. Results: ccRCC TIC appeared rare from injected suspensions, but xenografts engrafted frequently from tiny fragments, and clonogenic frequencies were 103-104greater than TIC frequencies, suggesting that LDAs underestimated ccRCC tumor cell potential. We systematically identified multiple methodological steps that distort quantitation and identification of ccRCC TIC. For example cell viability was highly variable prior to processing, disaggregation itself destroyed up to 99% of tumor cells, standard assays substantially overestimated tumor cell viability in suspensions, and supplementation with human extracellular cells or proteins, or inhibition of anoikis by Y-26732 increased clonogenic and TIC frequencies in cell lines and primary ccRCC suspensions. Annexin-V staining revealed that tumor cells were more apoptotic then normal stromal cells, and that tumor cells positive for CD44 (a putative CSC marker) were more viable than CD44- tumor cells. Conclusions: We describe multiple, unappreciated and largely unavoidable observational errors in essential methods used to study TIC in ccRCC. ccRCC TIC may be more common than appreciated. Re-examination of the CSC hypothesis in other solid tumors is warranted in view of these previously unexplored methodological biases.

scholarly journals Homologous tumor cell membrane vesicles active preferential self-recognition of tumor cells in vitro

2022 ◽  
Vol 65 (1) ◽  
Author(s):  
Chenghu Wu ◽  
Ailin Yu ◽  
Yue Chen ◽  
Mingbo Fan
Keyword(s):  
Cell Membrane ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Tumor Therapy ◽  
Membrane Vesicles ◽  
Membrane System ◽  
Tumor Cell Membrane ◽  
Self Recognition

AbstractCell membrane vesicles, as delivery carriers of drugs or biological agents in vivo, are an important therapeutic mode in the study of disease treatment. Tumor membrane-derived vesicles have been widely used in tumor therapy because of their good tumor enrichment effect. The most common method is the surface of nanoparticles coated with tumor cell membrane, which can effectively prolong the circulation time of particles in the blood and the enrichment of tumors. In this study, we prepared vesicles of different tumor cell membrane derivate and studied their targeting to tumors detailly. The results showed that homologous vesicles have high targeting to homologous tumor cells. The fluorescence of vesicles in homologous tumor cells was significantly higher than that in other tumor cells. This study will provide a new strategy and guidance for the clinical treatment of cancer based on the tumor cell membrane system. Graphical Abstract

scholarly journals Comparison of the Effects of Fucoidans on the Cell Viability of Tumor and Non-Tumor Cell Lines

Marine Drugs ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. 441 ◽  
Author(s):  
Bittkau ◽  
Dörschmann ◽  
Blümel ◽  
Tasdemir ◽  
Roider ◽  
...  
Keyword(s):  
Cell Viability ◽  
Tumor Cells ◽  
Cell Lines ◽  
Biological Activities ◽  
Tumor Therapy ◽  
Age Related Macular Degeneration ◽  
Saccharina Latissima ◽  
Total Phenolic ◽  
Age Related ◽  
Hct 116

Fucoidans extracted from brown algae exert manifold biological activities paving the way for the development of numerous applications including treatments outside tumor therapy such as age-related macular degeneration or tissue engineering. In this study, we investigated the antiproliferative effects of fucoidans extracted from six different algae (Fucus vesiculosus, F. serratus, F. distichus subsp. evanescens, Dictyosiphon foeniculaceus, Laminaria digitata, Saccharina latissima) as well as three reference compounds (Sigma fucoidan, heparin, enoxaparin) on tumor (HL-60, Raji, HeLa, OMM-1, A-375, HCT-116, Hep G2) and non-tumor (ARPE-19, HaCaT) cell lines. All fucoidans were extracted according to a standardized procedure and tested in a commercially available MTS assay. Cell viability was measured after 24 h incubation with test compounds (1–100 µg/mL). Apart from few exceptions, fucoidans and heparins did not impair cell viability. In contrast, fucoidans significantly increased cell viability of suspension cell lines, but not of adherent cells. Fucoidans slightly increased viability of tumor cells and had no impact on the viability of non-tumor cells. The cell viability of HeLa and ARPE-19 cells negatively correlated with protein content and total phenolic content (TPC) of fucoidans, respectively. In summary, none of the tested fucoidans turned out to be anti-proliferative, rendering them interesting for future studies and applications.

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