scholarly journals PHARMACOLOGICAL EFFECT OF AMINOFERROCENE IN MICE WITH L1210 LEUKEMIA

2015 ◽  
Vol 37 (2) ◽  
pp. 120-125 ◽  
Author(s):  
V F Chekhun ◽  
A Mokhir ◽  
S Daum ◽  
I Todor ◽  
N Yu Lukianova ◽  
...  
Keyword(s):  
Biological Effects ◽  
Leukemia Cell ◽  
Annexin V ◽  
Active Species ◽  
L1210 Leukemia ◽  
Lymphoid Leukemia ◽  
Thiol Compounds ◽  
Free Iron ◽  
Nonprotein Thiol

Aim: To study the cytostatic and some biological effects of aminoferrocene using mice with L1210 lymphoid leukemia. Materials and Methods: Experiments were performed on BDF1 male mice (DBA/2, female × C57Bl/6, male) with transplantable L1210 lymphoid leukemia. Determination of antitumor activity of Benzyl-Fc Boron (Bn), it was injected intraperitoneally 6 times daily, starting on day 2 after L1210 leukemia cell transplantation. Doses of Bn such as 26; 260 and 2600 μg/kg were used. The determination of intracellular content of cardiolipin, thiols, reactive oxygen species (ROS) and also analysis of Annexin V positivity and mitochondrial transmembrane potential (JC-1 staining) were performed with use of flow cytometry. The levels of “free iron” complexes, transferrin active forms and the rate of NO generation were measured by EPR-specroscopy. Results: Six daily injections of Bn at a dose of 26 μg/kg resulted in an increased survival of mice with L1210 leukemia by 28% (p < 0.05). Bn led to an increase of apoptotic cells number and ROS amount in leukemia cells. Besides, Bn caused a decrease of cardiolipin and nonprotein thiol compounds content. The membrane electrochemical potential of cell mitochondria was decreased also after Bn administration. Studies using EPR-spectroscopy revealed a significant increase in a level of “free iron”, content of transferrin active species and generation rate of NO by inducible NO-synthase in L1210 cells after aminoferrocene administration. Conclusion: Our data indicate that Benzyl-Fc Boron can be promising candidate for realizing a new strategy of anticancer therapy with the use of ROS-inducing agents.

The BCL-2 Antagonist ABT-737 Is Highly Effective on Primary Acute Lymphoblastic Leukemia Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 155-155
Author(s):  
Maria Rosaria Ricciardi ◽  
Chiara Gregorj ◽  
Fabiana De Cave ◽  
Paola Bergamo ◽  
Samantha Decandia ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Lymphoblastic Leukemia ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Annexin V ◽  
Lymphoid Leukemia ◽  
Childhood All ◽  
Leukemia Cell Lines

Abstract The treatment of adult acute lymphoblastic leukemia (ALL) remains unsatisfactory. A potential hope is now given to Philadelphia-positive cases by targeted treatment modalities. Among other pathways involved in cell proliferation, we have recently demonstrated (Blood2007; 109:5473) the unfavorable role of ERK1/2 phosphorylation as an independent predictor of complete remission (CR) in adult ALL, suggesting the potential therapeutic value of other targeted therapies. The B-cell leukemia/lymphoma 2 (Bcl-2) family of proteins are important regulators of apoptosis and are frequently found aberrantly expressed, particularly in lymphoid malignancies. The role of Bcl-2 overexpression in tumorigenesis and chemoresistance prompted us to investigate whether the inhibition of the antiapoptotic function may result also in ALL in an attractive therapeutic strategy. In this study, we thus investigated the cell cycle and apoptotic effects of ABT-737 (kindly provided by Abbott Laboratories), a Bcl-2 (BH3) inhibitor, on both lymphoid leukemia cell lines and primary adult and childhood ALL cells. The lymphoid leukemia cell lines CEM and MOLT-4 were exposed to increasing concentrations of ABT-737 (from 0.1 to 1 μM) up to 72 hours. A dose- and time-dependent cell growth arrest and induction of apoptosis was found. In fact, measuring the subG0/1 peak at 48 hours, the levels of apoptosis increased in the CEM cell line from 14.1% (DMSO) to 34.4%, 64.5%, 86.5% and 98.6% at ABT-737 concentrations of 0.1, 0.25, 0.5 and 1 μM, respectively. Similarly, 48 hours of exposure to ABT-737 increased in MOLT-4 the Annexin V-positive cells from 7.2% to 64.2%. The effects of ABT-737 were then examined on primary blasts from 9 ALL patients (6 adults and 3 children). Bone marrow aspirates with a blast infiltration &gt;70% were obtained at diagnosis from patients broadly characterized for clinical and biological parameters, as well as therapeutic response. ALL cells were cultured in vitro with ABT-737 (at increasing concentrations from 0.01 to 1 μM) for 24 hours. A significant decrease in viability was observed at 0.01 μM (p=0.008) with a remarkable dose-dependent increase of apoptosis. In fact, Annexin V-positive cells increased from a mean baseline value of 16.8% ± 8.8 to 43.6% ± 22.8 (p=0.04), 66% ± 21.3 (p=0.0001), 70.3% ± 26.9 (p=0.04), 74.6% ± 18.9 (p=0.03) and 76.2% ± 11.8 (p&lt;0.0001) in the presence of ABT-737 at 0.01, 0.1, 0.25, 0.5 and 1 μM, respectively. A significant cell killing was demonstrated in all samples (9/9), including Ph-positive ALL. No significant cell cycle changes were instead detected even at higher concentration of ABT-737. In summary, our study shows for the first time a potent growth-inhibitory and pro-apoptotic activity of the Bcl-2 antagonist ABT-737, at nanomolar concentrations, on primary cells from adult and childhood ALL samples. These results prompt to further extend pre-clinical studies in the different biologically-defined subset of ALL and suggest a potential clinical development of a Bcl-2 family inhibitor in this disease.

scholarly journals SALL4 is a key regulator of survival and apoptosis in human leukemic cells

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 805-813 ◽  
Author(s):  
Jianchang Yang ◽  
Li Chai ◽  
Chong Gao ◽  
Taylor C. Fowles ◽  
Zaida Alipio ◽  
...  
Keyword(s):  
Stem Cell ◽  
Leukemia Cell ◽  
Annexin V ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Immunodeficient Mice ◽  
Leukemia Cell Lines ◽  
Human Leukemic Cells ◽  
Cell Phenotypes ◽  
Proliferation Assays

Abstract Increasing studies suggest that SALL4 may play vital roles in leukemogenesis and stem cell phenotypes. We have mapped the global gene targets of SALL4 using chromatin immunoprecipitation followed by microarray hybridization and identified more than 2000 high-confidence, SALL4-binding genes in the human acute promyelocytic leukemic cell line, NB4. Analysis of SALL4-binding sites reveals that genes involved in cell death, cancer, DNA replication/repair, and cell cycle were highly enriched (P < .05). These genes include 38 important apoptosis-inducing genes (TNF, TP53, PTEN, CARD9, CARD11, CYCS, LTA) and apoptosis-inhibiting genes (Bmi-1, BCL2, XIAP, DAD1, TEGT). Real-time polymerase chain reaction has shown that expression levels of these genes changed significantly after SALL4 knockdown, which ubiquitously led to cell apoptosis. Flow cytometry revealed that reduction of SALL4 expression in NB4 and other leukemia cell lines dramatically increased caspase-3, annexin V, and DNA fragmentation activity. Bromodeoxyuridine-incorporation assays showed decreased numbers of S-phase cells and increased numbers of G1- and G2-phase cells indicating reduced DNA synthesis, consistent with results from cell proliferation assays. In addition, NB4 cells that express low levels of SALL4 have significantly decreased tumorigenecity in immunodeficient mice. Our studies provide a foundation in the development of leukemia stem cell–specific therapy by targeting SALL4.

Effect of (dl)-5-methyltetrahydrofolate on lymphoid leukemia cell lines

1991 ◽  
Vol 15 (7) ◽  
pp. 645-649 ◽  
Author(s):  
Pietro Antonio Bernabei ◽  
William I. Bensinger
Keyword(s):  
Cell Lines ◽  
Leukemia Cell ◽  
Lymphoid Leukemia ◽  
Leukemia Cell Lines

Characteristics of folic acid transport in the L1210 leukemia cell

1969 ◽  
Vol 193 (2) ◽  
pp. 456-467 ◽  
Author(s):  
Norman S. Lichtenstein ◽  
Vincent T. Oliverio ◽  
I.David Goldman
Keyword(s):  
Folic Acid ◽  
Leukemia Cell ◽  
L1210 Leukemia ◽  
Acid Transport

Two-way trafficking of Annexin V positive cells between mother and fetus: determination of apoptosis at delivery

2007 ◽  
Vol 27 (4) ◽  
pp. 348-351 ◽  
Author(s):  
A. Kolialexi ◽  
G.Th Tsangaris ◽  
A. Anagnostopoulos ◽  
D. Chondros ◽  
V. Bagiokos ◽  
...  
Keyword(s):  
Annexin V

scholarly journals Stimulation of Erythrocyte Cell Membrane Scrambling by C-Reactive Protein

2017 ◽  
Vol 41 (2) ◽  
pp. 806-818 ◽  
Author(s):  
Majed Abed ◽  
Christian Thiel ◽  
Syeda T. Towhid ◽  
Kousi Alzoubi ◽  
Sabina Honisch ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Healthy Volunteers ◽  
Annexin V ◽  
Caspase Activation ◽  
C Reactive Protein ◽  
Forward Scatter ◽  
Reactive Protein ◽  
Phosphatidylserine Translocation ◽  
Binding Cell

Background: Eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phosphatidylserine-translocation, is triggered by fever and inflammation. Signaling includes increased cytosolic Ca2+-activity ([Ca2+]i), caspase activation, and ceramide. Inflammation is associated with increased plasma concentration of C-reactive protein (CRP). The present study explored whether CRP triggers eryptosis. Methods: Phosphatidylserine abundance at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ceramide abundance and caspase-3-activity utilizing FITC-conjugated antibodies. Moreover, blood was drawn from patients with acute appendicitis (9♀,11♂) and healthy volunteers (10♀,10♂) for determination of CRP, blood count and phosphatidylserine. Results: A 48h CRP treatment significantly increased the percentage of annexin-V-binding cells (≥5µg/ml), [Ca2+]i (≥5µg/ml), ceramide (20µg/ml) and caspase-activity (20µg/ml). Annexin-V-binding was significantly blunted by caspase inhibitor zVAD (10µM). The percentage of phosphatidylserine-exposing erythrocytes in freshly drawn blood was significantly higher in appendicitis patients (1.83±0.21%) than healthy volunteers (0.81±0.09%), and significantly higher following a 24h incubation of erythrocytes from healthy volunteers to patient plasma than to plasma from healthy volunteers. The percentage of phosphatidylserine-exposing erythrocytes correlated with CRP plasma concentration. Conclusion: C-reactive protein triggers eryptosis, an effect at least partially due to increase of [Ca2+]i, increase of ceramide abundance and caspase activation.

scholarly journals RESEARCH OF THE SYNTHETIC, PHYSICAL AND CHEMICAL PROPERTIES OF 3-ALKYLSULFONYL-5-(CHINOLINE-2-YL, 2-HYDROXYCHINOLINE-4-YL)-4-R -2,4-DIHYDRO3N-1,2,4-TRIAZOLES 1

2016 ◽  
Vol 10 (1) ◽  
pp. 81
Author(s):  
Kaplaushenko Tm ◽  
Panasenko Oi ◽  
Kucheryavy Yu
Keyword(s):  
Biological Effects ◽  
Chemical Properties ◽  
Biological Action ◽  
Pharmacological Properties ◽  
Physical And Chemical Properties ◽  
Element Analysis ◽  
Fundamental Research ◽  
Physical And Chemical ◽  
And Chemical Properties

ABSTRACTObjective: Fundamental research in pharmacy and medicine have shown that drugs, which are based on nucleus of the 1,2,4-triazole, have a widerange of biological effects. Derivatives of this heterocyclic system have well-known Ukrainian clinicians and the world scientists due to its antifungal,antidepressant, anticancer, cardio- and hepatoprotective properties. The pharmacological activity of most organic compounds depends on severaldifferent factors, including bioavailability of the substance. Hence, it is very important to consider the results of the synthetic and biological researchesand established dependence of structure on the biological action when scientists model new molecules or improve pharmacological properties of anexisting structure. One of the important social and economic problems of the pharmaceutical industry is the implementation in practice of new drugsthat could compete with expensive imported drugs. In recent times, 1,2,4-triazole-3-thioderivatives take attention of compatriots and scientists offoreign countries who are working on finding bioactive compounds including heterocyclic systems. The structure, physical and chemical properties,pharmacological activities of 1,2,4-triazoles, and their 3-thioderivatives are understudied. Hence, the study of that will be actually and novelty formodern science. The main purpose of our research is synthesis of 3-alkylsulfonyl-5-(chinoline-2-yl, 2-hydroxychinoline-4-yl)-4-R-2,4-dihydro-3N1,2,4-triazoles,studyingof its physicaland chemical properties.Methods: The initial compounds have been synthesized previously using known in literature techniques. Oxidation of the sulfur atom of thesynthesized compounds to the hexavalent condition was carried out adding solution of hydrogen peroxide.Results: The structure of the obtained compounds was determined with the modern physical and chemical analysis methods: Element analysis,infrared-spectrophotometry, and their individuality with thin layer chromatography.Conclusions: Prospect of the further researches is determination of acute toxicity and next studying of pharmacological properties of the synthesizedcompounds.Keywords: 1,2,4-triazoles, Synthesis, Chemical properties, Chinoline.1 

scholarly journals Differential Effects of Polyphenols on Proliferation and Apoptosis in Human Myeloid and Lymphoid Leukemia Cell Lines

2013 ◽  
Vol 13 (10) ◽  
pp. 1601-1613 ◽  
Author(s):  
Amani Mahbub ◽  
Christine Maitre ◽  
Sarah Haywood-Small ◽  
Gordon McDougall ◽  
Neil Cross ◽  
...  
Keyword(s):  
Cell Lines ◽  
Leukemia Cell ◽  
Lymphoid Leukemia ◽  
Differential Effects ◽  
Leukemia Cell Lines ◽  
Proliferation And Apoptosis
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