scholarly journals PAR4-Mediated PI3K/Akt and RhoA/ROCK Signaling Pathways Are Essential for Thrombin-Induced Morphological Changes in MEG-01 Cells

2022 ◽  
Vol 23 (2) ◽  
pp. 776
Author(s):  
Yunkyung Heo ◽  
Hyejin Jeon ◽  
Wan Namkung
Keyword(s):  
Signaling Pathways ◽  
Kinase Inhibitors ◽  
Morphological Changes ◽  
Leukemia Cell ◽  
Selective Inhibition ◽  
Underlying Mechanism ◽  
Transient Signal ◽  
Leukemia Cell Line ◽  
Receptor System

Thrombin stimulates platelets via a dual receptor system of protease-activated receptors (PARs): PAR1 and PAR4. PAR1 activation induces a rapid and transient signal associated with the initiation of platelet aggregation, whereas PAR4 activation results in a prolonged signal, required for later phases, that regulates the stable formation of thrombus. In this study, we observed differential signaling pathways for thrombin-induced PAR1 and PAR4 activation in a human megakaryoblastic leukemia cell line, MEG-01. Interestingly, thrombin induced both calcium signaling and morphological changes in MEG-01 cells via the activation of PAR1 and PAR4, and these intracellular events were very similar to those observed in platelets shown in previous studies. We developed a novel image-based assay to quantitatively measure the morphological changes in living cells, and observed the underlying mechanism for PAR1- and PAR4-mediated morphological changes in MEG-01 cells. Selective inhibition of PAR1 and PAR4 by vorapaxar and BMS-986120, respectively, showed that thrombin-induced morphological changes were primarily mediated by PAR4 activation. Treatment of a set of kinase inhibitors and 2-aminoethoxydiphenyl borate (2-APB) revealed that thrombin-mediated morphological changes were primarily regulated by calcium-independent pathways and PAR4 activation-induced PI3K/Akt and RhoA/ROCK signaling pathways in MEG-01 cells. These results indicate the importance of PAR4-mediated signaling pathways in thrombin-induced morphological changes in MEG-01 cells and provide a useful in vitro cellular model for platelet research.

scholarly journals Cytotoxic activity of ethanolic extracts of Eleutherococcus species cultivated in Poland on HL60 leukemia cell line

2014 ◽  
Vol 27 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Daniel Zaluski ◽  
Helena Danuta Smolarz ◽  
Anna Bogucka-Kocka
Keyword(s):  
Cytotoxic Activity ◽  
Cell Line ◽  
Morphological Changes ◽  
Leukemia Cell ◽  
Ethanol Extract ◽  
Leukemia Cell Line ◽  
Lymphoid Leukemia ◽  
Ethanolic Extracts ◽  
Ic50 Values

Abstract The Eleutherococcus species including 40 species native to Asia are medicinal plants widely used in traditional medicine. Some of these species are cultivated at the botanical gardens in Europe. On the basis on our earlier studies it was concluded that the extracts of analyzed species act as antioxidants, inhibitors of MMPs, and cytotoxic against Jurkat 45 leukemia cell line. In this study, the anti-leukemic potential of roots and leaves from six Eleutherococcus species cultivated in Poland was determined. The in vitro cytotoxic activity towards human promyelotic leukemia cell line HL60 using trypan blue assay was evaluated. The induction of apoptosis in stimulated leukemia cells was determined by AnnexinV method. Morphological changes in treated cells were observed by microscopic investigations. The results showed that ethanolic extracts from the roots and the leaves of E. senticosus, E. setchuensis, E. sessiliflorus, E.gracilistylus, E. henryi and E. divaricatus exhibit cytotoxic effect towards leukemic HL60 cells. The received IC50 values for roots ranged from 49- 208 μg/mL and for the leaves from 116-518 μg/mL. The ethanol extract from the roots of E. divaricatus showed the highest cytotoxic and proapoptotic effect on HL60 human lymphoid leukemia cell line.

scholarly journals Facile synthesis of Au/ZnO/Ag nanoparticles using Glechoma hederacea L. extract, and their activity against leukemia

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Renata Dobrucka ◽  
Aleksandra Romaniuk-Drapała ◽  
Mariusz Kaczmarek
Keyword(s):  
Electron Microscopy ◽  
Ag Nanoparticles ◽  
Mononuclear Cells ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Mtt Test ◽  
Transmission Electron ◽  
Almost All ◽  
Glechoma Hederacea

AbstractMetal combinations have been attracting the attention of scientists for some time. They usually exhibit new characteristics that are different from the ones possessed by their components. In this work, Au/ZnO/Ag nanoparticles were synthesized biologically using Glechoma hederacea L. extract. The synthesized Au/ZnO/Ag nanoparticles were characterized by UV-Vis, Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM), and Atomic Force Microscopy (AFM). The microscopic methods confirmed the presence of spherical nanoparticles of 50–70 nm. The influence of biologically synthesized Au/ZnO/Ag nanoparticles on the vitality of human cells was evaluated in vitro with the use of established human Acute T Cell Leukemia cell line, Jurkat (ATCC® TIB-152™), as well as mononuclear cells isolated from peripheral blood (PBMC) of voluntary donors. Cell survival and the half-maximal inhibitory concentration index (IC50) were analyzed by the MTT test. The studies showed that the total loss of cell viability occurred at the Au/ZnO/Ag nanoparticle concentration range of 10 µmol–50 µmol. The use of Au/ZnO/Ag nanoparticles at the concentration of 100 µmol eliminated almost all living cells from the culture in 24h. The above observation confirms the result obtained during the MTT test.

The Human Leukemic HL-60 Cell Line: An in Vitro Model for Cell Death Endpoint Identification

1996 ◽  
Vol 24 (4) ◽  
pp. 581-587
Author(s):  
Cristiana Zanetti ◽  
Arrnalaura Stammati ◽  
Orazio Sapora ◽  
Flavia Zucco
Keyword(s):  
Cell Death ◽  
Cell Line ◽  
In Vitro Model ◽  
Leukemia Cell ◽  
Promyelocytic Leukemia ◽  
Leukemia Cell Line ◽  
Cell Type ◽  
Vitro Model ◽  
Promyelocytic Leukemia Cell Line

The aim of this study was to investigate the endpoints related to cell death, either necrosis or apoptosis, induced by four chemicals in the promyelocytic leukemia cell line, HL-60. Cell morphology, DNA fragmentation, cytofluorimetric analysis and oxygen consumption were used to classify the type of cell death observed. In our analysis, we found that not all the selected parameters reproduced the differences observed in the cell death caused by the four chemicals tested. As cell death is a very complex phenomenon, several factors should be taken into account (cell type, exposure time and chemical concentration), if chemicals are to be classified according to differences in the mechanisms more directly involved in cell death.

scholarly journals Normal functional characteristics of cultured human promyelocytic leukemia cells (HL-60) after induction of differentiation by dimethylsulfoxide.

1979 ◽  
Vol 149 (4) ◽  
pp. 969-974 ◽  
Author(s):  
S J Collins ◽  
F W Ruscetti ◽  
R E Gallagher ◽  
R C Gallo
Keyword(s):  
Leukemia Cell ◽  
Myeloid Cell ◽  
Promyelocytic Leukemia ◽  
Leukemia Cell Line ◽  
Functional Characteristics ◽  
Dye Reduction ◽  
Normal Functional ◽  
Vitro Model ◽  
Promyelocytic Leukemia Cell Line

The HL-60 human promyelocytic leukemia cell line can be induced to terminally differentiate to mature myeloid cells sharing a number of functional characteristics with normal granulocytes including response to chemoattractants, development of complement receptors, phagocytosis, superoxide production, and nitroblue tetrazolium dye reduction. Hence the Me2SO-induced HL-60 cells provide a unique in vitro model for studying various important aspects of human myeloid cell differentiation.

scholarly journals Human Platelets Effectively Kill K-562 Cells, a Chronic Myelogenic Leukemia Cell Line,in vitro

1990 ◽  
Vol 81 (5) ◽  
pp. 449-453 ◽  
Author(s):  
Terutaka Sagawa ◽  
Takeshi Kodama ◽  
Akio Tominaga ◽  
Mariko Okada
Keyword(s):  
Cell Line ◽  
Leukemia Cell ◽  
Human Platelets ◽  
Leukemia Cell Line ◽  
K 562 Cells

scholarly journals (Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

2021 ◽  
Vol 17 ◽  
pp. 2260-2269
Author(s):  
Luiz Claudio Ferreira Pimentel ◽  
Lucas Villas Boas Hoelz ◽  
Henayle Fernandes Canzian ◽  
Frederico Silva Castelo Branco ◽  
Andressa Paula de Oliveira ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Competitive Inhibition ◽  
Leukemia Cell ◽  
Docking Studies ◽  
Leukemia Cell Line ◽  
Inhibition Mechanism ◽  
Triazole Derivatives

The enzyme tyrosine kinase BCR-Abl-1 is the main molecular target in the treatment of chronic myeloid leukemia and can be competitively inhibited by tyrosine kinase inhibitors such as imatinib. New potential competitive inhibitors were synthesized using the (phenylamino)pyrimidine-pyridine (PAPP) group as a pharmacophoric fragment, and these compounds were biologically evaluated. The synthesis of twelve new compounds was performed in three steps and assisted by microwave irradiation in a 1,3-dipolar cycloaddition to obtain 1,2,3-triazole derivatives substituted on carbon C-4 of the triazole nucleus. All compounds were evaluated for their inhibitory activities against a chronic myeloid leukemia cell line (K562) that expresses the enzyme tyrosine kinase BCR-Abl-1 and against healthy cells (WSS-1) to observe their selectivity. Three compounds showed promising results, with IC50 values between 1.0 and 7.3 μM, and were subjected to molecular docking studies. The results suggest that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One compound showed the greatest interaction affinity for BCR-Abl-1 in the docking studies.

scholarly journals A combination of a T cell-derived lymphokine differentiation-inducing activity and a physiologic concentration of retinoic acid induces HL-60 to differentiate to cells with functional chemotactic peptide receptors

Blood ◽  
1986 ◽  
Vol 67 (5) ◽  
pp. 1273-1280
Author(s):  
M Imaizumi ◽  
TR Breitman
Keyword(s):  
Retinoic Acid ◽  
T Cell ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Chemotactic Peptide ◽  
Phagocytic Cells ◽  
Peptide Receptors ◽  
Morphologic Characteristics ◽  
O2 Production

The human acute promyelocytic leukemia cell line HL-60 is induced by retinoic acid (RA) and N,N-dimethylformamide (DMF) to differentiate into cells having many of the functional and morphologic characteristics of mature granulocytes. With normal human phagocytic cells there is both superoxide anion (O2-) production and chemotaxis in response to chemoattractants such as N-formyl-methionyl-leucyl- phenylalanine (FMLP). We have now found that although HL-60 cells induced with RA alone produce O2- in response to 12–0-tetradecanoyl- phorbol-13-acetate (TPA) they are deficient in FMLP-stimulated O2- production and chemotaxis. In contrast, HL-60 induced either with DMF or with a combination of 10 nmol/L RA and a T cell-derived lymphokine, differentiation-inducing activity (DIA), produce O2- and exhibit chemotaxis in response to FMLP. The basis for these results appears to be the concentration of cell surface chemotactic peptide receptors. Thus, untreated HL-60 and HL-60 induced with either RA alone or DIA alone do not have measurable levels of FMLP receptors, whereas HL-60 induced with a combination of RA and DIA has 5,400 receptors per cell. HL-60 induced with RA and DIA plus 1 mumol/L dexamethasone have 25,000 receptors per cell and have greater chemotactic activity than HL-60 induced with the combination of RA and DIA. Thus, differentiation of HL- 60 to cells with many properties of normal phagocytes can be induced in vitro by physiologic substances.

SYNTHESIS, SPECTRAL CHARACTERIZATION AND ANTICANCER EVALUATION OF NEW DIAZENYL SCHIFF BASE DERIVATIVES

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (02) ◽  
pp. 20-28
Author(s):  
P. K. N. Sarangi ◽  
◽  
J. Sahoo ◽  
S. K Paidesetty ◽  
G. P. Mohanta
Keyword(s):  
Schiff Base ◽  
Anticancer Activity ◽  
Cell Line ◽  
Leukemia Cell ◽  
Cancer Cell Line ◽  
Leukemia Cell Line ◽  
Primary Amines ◽  
Schiff Base Derivatives ◽  
Mcf 7

A series of several diazenyl Schiff base derivatives were designed and synthesized through azo coupling of diazotised primary amines with the novel synthesized Schiff base ligand (E)-N-((2-chloroquinolin-3-yl) methylene)-4-phenylthiazol-2-amine. All the synthesized compounds have been analysed by different spectral techniques such as elemental analysis, 1H NMR, FT-IR, UV-Vis and LC-MS for their structural confirmation. The above conjugates have been studied for their solvent effects by treating them with different solvents. The results of in vitro cytotoxic study of the synthesized compounds against MCF 7 (human breast cancer cell line) and K562 (Chronic Myeloid Leukemia cell line) revealed that some of the compounds show cytotoxic effect. However, the compounds (NZ)-N-(((4-bromo-3-methylphenyl) diazenyl) (2-chloroquinolin-3-yl) methylene)-4-phenylthiazol-2-amine: (5d) and 4-(((Z)-(2-chloroquinolin-3- yl)(4-phenylthiazol-2-ylimino)methyl)diazenyl)phenol (5e) showed potent cytotoxic activity in comparison to other compounds against MCF 7. Corroborating the results of anticancer activity, it is found to be observed that the compound 4- (((Z)- (2-chloroquinolin-3-yl) (4-phenylthiazol-2-ylimino)methyl) diazenyl) phenol (5e) showed excellent anticancer activity against MCF 7, which is further justified by the apoptosis study through Annexin V-FITC/PI analysis.

scholarly journals Mitosis in Cancer Cell Increases Immune Resistance via High Expression of HLA-G and PD-L1

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2661
Author(s):  
Matti Ullah ◽  
Warda Aoudjeghout ◽  
Cynthia Pimpie ◽  
Marc Pocard ◽  
Massoud Mirshahi
Keyword(s):  
Protein Expression ◽  
Cancer Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
G1 Phase ◽  
G2 Phase ◽  
The Impact

Cancer is a result of “aggressive” division and uncontrolled proliferation of the abnormal cells that survive attack by immune cells. We investigated the expression of HLA-G and PD-L1 with the different stages of cancer cell division along with their role in the interaction of immune cells in vitro. Ovarian cancer (OVCAR-3) and chronic myeloid leukemia cell line (K-562) are used for this study. The correlation of protein expression with percentage of cells in each phase (G1, S and G2 phase) was evaluated through FACS. Cells were synchronized in G1, G2 and mitotic phase to evaluate gene (RT-qPCR) and protein expression (FACS). Real-time immune cell attack (RTICA) analysis with PBMCs (peripheral blood mono-nuclear cells) and cancer cells were performed. We found that cells expressing higher levels of HLA-G and PD-L1 are mainly in G2 phase and those expressing lower levels are mainly in G1 phase. Evidently, the higher expression of the two proteins was observed when synchronized in mitotic phase as compared to low expression when synchronized in G1 phase. RTICA analysis showed the presence of HLA-G delayed the lysis of the cells. In conclusion, the cancer cell can escape from immune cells in division stage that suggests the impact of mitosis index for cancer immunotherapy.

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