DNA binding, cytotoxic effects and probable targets of an oxindolimine–vanadyl complex as an antitumor agent

2019 ◽  
Vol 43 (45) ◽  
pp. 17831-17840 ◽  
Author(s):  
Bruno Soares Dario ◽  
Francisco Fernandes Neto ◽  
Marcelo Cecconi Portes ◽  
Rodrigo Boni Fazzi ◽  
Daniel Rodrigues da Silva ◽  
...  
Keyword(s):  
Dna Binding ◽  
Antitumor Agent ◽  
Cytotoxic Effects ◽  
Vanadyl Complex

The vanadyl–oxindolimine complex as an antitumor agent.

scholarly journals Cytotoxicity of Environmentally Relevant Concentrations of Aluminum in Murine Thymocytes and Lymphocytes

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Jamal Kamalov ◽  
David O. Carpenter ◽  
Irina Birman
Keyword(s):  
Flow Cytometry ◽  
Cell Death ◽  
Immune System ◽  
Dna Binding ◽  
Aluminum Chloride ◽  
Cell Swelling ◽  
Cytotoxic Effects ◽  
Minute Exposure ◽  
Low Concentrations ◽  
Dose Dependent

The effects of low concentrations of aluminum chloride on thymocytes and lymphocytes acutely dissociated from young mice were studied using flow cytometry with a DNA-binding dye. We demonstrate a rapid and dose-dependent injury in murine thymocytes and lymphocytes resulting from exposure to aluminum, as indicated by an increase in the entry into the cell of the DNA-binding dye, propidium iodine. A 60-minute exposure to 10 μM AlCl3caused damage of about 5% of thymocytes, while 50% were injured after 10 minutes at 20 μM. Nearly all thymocytes showed evidence of damage at 30 μM AlCl3after only 5 minutes of incubation. In lymphocytes, injury was observed at 15 μM AlCl3and less than 50% of cells were injured after a 60-minute exposure to 20 μM. Injury only rarely proceeded to rapid cell death and was associated with cell swelling. These results suggest that aluminum has cytotoxic effects on cells of the immune system.

scholarly journals Cytotoxic Effects of Resveratrol, Rutin and Rosmarinic Acid on ARH–77 Human (Multiple Myeloma) Cell Line

2016 ◽  
Vol 11 (10) ◽  
pp. 1934578X1601101 ◽  
Author(s):  
Zerrin Canturk ◽  
Miris Dikmen ◽  
Oge Artagan ◽  
Mustafa Guclu Ozarda ◽  
Nilgun Ozturk
Keyword(s):  
Multiple Myeloma ◽  
Rosmarinic Acid ◽  
Antitumor Agent ◽  
Myeloma Cell ◽  
Artemia Salina ◽  
Polyphenolic Compounds ◽  
Control Group ◽  
Mitochondrial Activity ◽  
Cytotoxic Effects ◽  
Hematological Cancers

Multiple myeloma (MM) cancers are 10% of hematological cancers. Leukemia ARH-77 is a malignancy like MM with a worse course of disease and the survival rate from it is very low. Therefore, ARH-77 is a commonly used model for antitumor agent studies. Polyphenolic compounds, such as resveratrol, rutin and rosmarinic acid, have many protective roles, but there is no comparative study about these three polyphenolic compounds on ARH-77. In the present study, we investigated the cytotoxic effects of resveratrol, rutin and rosmarinic acid on ARH-77. Toxic concentration ranges were determined by the brine shrimp lethality test on Artemia salina. In addition, for determination of their cytotoxic effects, MTT and NR methods were used for ARH-77. Resveratrol caused significant reduction in both mitochondrial and lysosomal activities compared with the control group. Maximum inhibition values were detected on mitochondrial and lysosomal activity with 200 μM concentrations after 48 hours. After a 24 hours incubation period, rutin showed cytotoxic effects, particularly with 50, 100 and 200 μM concentrations. Rosmarinic acid also decreased the mitochondrial activity with the same concentrations. Resveratrol showed higher cytotoxic effects than rutin and rosmarinic acid. According to our study, polyphenolic compounds such as rutin, resveratrol and rosmarinic acid may hold promise in multiple myeloma treatment with further investigations.

Selective cellular uptake and retention of SN 28049, a new DNA-binding topoisomerase II-directed antitumor agent

2014 ◽  
Vol 74 (1) ◽  
pp. 25-35 ◽  
Author(s):  
Ying Yi Chen ◽  
Pradeep B. Lukka ◽  
Wayne R. Joseph ◽  
Graeme J. Finlay ◽  
James W. Paxton ◽  
...  
Keyword(s):  
Dna Binding ◽  
Cellular Uptake ◽  
Topoisomerase Ii ◽  
Antitumor Agent

Inhibition of mammalian ribonucleotide reductase by cis-diamminedichloroplatinum(II)

1992 ◽  
Vol 70 (12) ◽  
pp. 1332-1338 ◽  
Author(s):  
Christine S. M. Chiu ◽  
Arthur K. Chan ◽  
Jim A. Wright
Keyword(s):  
Drug Resistance ◽  
Ribonucleotide Reductase ◽  
Reductase Activity ◽  
Mutant Cell ◽  
Antitumor Agent ◽  
Resistance Mechanisms ◽  
Point Of View ◽  
Cytotoxic Action ◽  
Cytotoxic Effects ◽  
Ribonucleotide Reductase Activity

Ribonucleotide reductase is a highly regulated, rate-limiting activity in the synthesis of DNA. A previous study has shown that the Escherichia coli enzyme is inhibited by the clinically important antitumor agent cis-diamminedichloroplatinum(II) (DDP), and this has led to the hypothesis that ribonucleotide reductase is an important site of action for this chemotherapeutic agent. This hypothesis has been directly tested in this investigation. We observed that DDP inhibits the mammalian ribonucleotide reductase, with 50% inhibition occurring at 0.3 mM. Unlike the E. coli enzyme where only one of the two protein components is targeted by DDP, we observed that both of the mammalian proteins (R1 and R2) were sites for the inhibitory activity of the drug. Colony-forming experiments, enzyme activity studies, and analyses of R1 and R2 message levels in mutant cell lines containing either high levels of ribonucleotide reductase activity or exhibiting resistance to the cytotoxic effects of DDP were used to further investigate the potential role of ribonucleotide reductase in DDP cytotoxic action and drug resistance. These studies did not support a hypothesis formulated in the earlier investigation that inhibition of ribonucleotide reductase is an important component of DDP cytotoxic activity or that it is a major participant in DDP resistance mechanisms. From a biological point of view, DDP is a very active drug, and in addition to its cytotoxic effects it is capable of inducing a variety of cellular changes. Whether or not the inhibition of mammalian ribonucleotide reductase activity that we have described in this study plays a role in mediating any of these other effects remains to be determined.Key words: cisplatin, ribonucleotide reductase, drug resistance, hydroxyurea.

scholarly journals Essential Role for Verotoxin in Sustained Stress-Activated Protein Kinase and Nuclear Factor Kappa B Signaling, Stimulated by Escherichia coli O157:H7 in Vero Cells

2002 ◽  
Vol 70 (10) ◽  
pp. 5370-5380 ◽  
Author(s):  
Pamela Cameron ◽  
Deborah Bingham ◽  
Andrew Paul ◽  
Martin Pavelka ◽  
Scott Cameron ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Protein Kinase ◽  
Dna Binding ◽  
Essential Role ◽  
Nuclear Factor Kappa B ◽  
Vero Cells ◽  
Nuclear Factor ◽  
Cytotoxic Effects ◽  
E Coli ◽  
Nuclear Factor Kappa

ABSTRACT The effects of Escherichia coli O157:H7 (strains E30480 and PM601) and the associated verotoxins (VTs), VT1 and VT2, on stress-activated protein kinase and nuclear factor kappa B (NF-κB) signaling were investigated with Vero cells, which are extremely sensitive to the cytotoxic effects of E. coli O157:H7 in vitro. Cell-free supernatants prepared from E30480 and PM601 cultures and purified VT1 and VT2 stimulated a strong and prolonged (>4-h) activation of both c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. However, JNK activity stimulated in response to E30480 supernatants was substantially reduced following pretreatment with anti-VT1 and anti-VT2 antibodies, while a VT1 and VT2 gene knockout mutant of PM601 was unable to stimulate JNK activity. E30480 supernatants also caused a sustained activation of NF-κB DNA binding, degradation of inhibitory kappa B alpha (IκBα), and an increase in inhibitory kappa B kinase α activity, although PM601 supernatants and VT1 and VT2 had no effect. However, preincubation with VTs prolonged the transient activation of NF-κB and IκBα degradation stimulated by either tumor necrosis factor alpha or interleukin 1β, while preincubation with anti-VT antibodies prevented the prolonged loss of IκBα and partially reduced DNA binding in response to E30480 supernatants. These results strongly suggest that in Vero cells, VT plays an essential role in sustained JNK and NF-κB signaling in response to E. coli O157:H7 and that this action may underpin their cell-selective cytotoxic effects. These studies also suggest that another component released by strain E30480 contributes to the early activation of JNK and NF-κB.

Sesquiterpene Lactones from Dimerostemma Species (Asteraceae) and in vitro Potential Anti-Inflammatory Activities

2006 ◽  
Vol 61 (9-10) ◽  
pp. 647-652 ◽  
Author(s):  
Ricardo Stefani ◽  
Karin Schorr ◽  
Juliana Maria Tureta ◽  
Walter Vichnewski ◽  
Irmgard Merfort ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Sesquiterpene Lactones ◽  
Raw 264.7 Cells ◽  
Structure Identification ◽  
Human Neutrophils ◽  
Raw 264.7 ◽  
Cytotoxic Effects ◽  
Anti Inflammatory

AbstractTwo Brazilian species of Dimerostemma (Asteraceae) were chemically investigated. Two known sesquiterpene lactones (STLs), a germacrolide and an eudesmanolide, were isolated from D. episcopale while D. brasilianum afforded the new germacranolide 1β,5β,10α-trihydroxy- 8α-angeloyloxy-germacra-3,11(13)-dien-6α,12-olide in addition to a known one. Structure identification based on NMR and MS analyses. 1β,10α,4α,5β-Diepoxy-8α-angeloyloxycostunolide isolated from D. brasilianum was studied for its anti-inflammatory activity. This STL completely inhibited DNA binding of the transcription factor NF-κB at a concentration of 5 μм and 10 μм in Jurkat T and Raw 264.7 cells, respectively. Elastase release from human neutrophils was reduced to 50% at a concentrations of 23 μм after stimulation with PAF and of 27 μм after stimulation with fMLP without showing cytotoxic effects. Additionally, elastase was also directly inhibited.

scholarly journals Novel Coumarin-Containing Aminophosphonatesas Antitumor Agent: Synthesis, Cytotoxicity, DNA-Binding and Apoptosis Evaluation

Molecules ◽  
2015 ◽  
Vol 20 (8) ◽  
pp. 14791-14809 ◽  
Author(s):  
Ya-Jun Li ◽  
Cai-Yi Wang ◽  
Man-Yi Ye ◽  
Gui-Yang Yao ◽  
Heng-Shan Wang
Keyword(s):  
Dna Binding ◽  
Antitumor Agent
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