Concanavalin A induces apoptosis in a dose‐dependent manner by modulating thiol/disulfide homeostasis in C6 glioblastoma cells

2021 ◽  
Author(s):  
Fatih Kar ◽  
Sedat Kacar ◽  
Ceyhan Hacioglu ◽  
Gungor Kanbak ◽  
Varol Sahinturk
Keyword(s):  
Concanavalin A ◽  
Dependent Manner ◽  
Glioblastoma Cells ◽  
Dose Dependent

scholarly journals Concanavalin A binding to human erythrocytes leads to alterations in properties of the membrane skeleton

1987 ◽  
Vol 241 (2) ◽  
pp. 521-525 ◽  
Author(s):  
S M Gokhale ◽  
N G Mehta
Keyword(s):  
Concanavalin A ◽  
Membrane Skeleton ◽  
Cross Linking ◽  
Dependent Manner ◽  
Con A ◽  
Normal Cells ◽  
Skeletal Protein ◽  
Low Ionic Strength ◽  
Dose Dependent ◽  
Resistance To Heat

Three properties related to the erythrocyte membrane skeleton are found to be altered after the binding of concanavalin A (Con A) to erythrocytes or their isolated membranes. Con A binding to normal erythrocytes imparts resistance to heat (49 degrees C)-induced fragmentation of the cells. The fragmentation, due to denaturation of spectrin at 49 degrees C, is prevented by Con A in a dose-dependent manner, but levels off at concentrations of Con A in excess of 100 micrograms/ml. The binding of Con A to ghosts isolated from normal, trypsin- or Pronase-treated cells prevents (completely or substantially) the elution of the skeletal protein complex when the membranes are extracted under low-ionic-strength conditions in the cold. The Con A-agglutinated membranes of trypsin- and Pronase-treated, but not normal, cells show cross-linking of skeletal proteins and band 3 with dimethyl adipimidate, a 0.86 nm (8.6 A)-span bifunctional reagent. The extent of cross-linking is greater in the Pronase-treated membrane than in the less-agglutinable trypsin-treated membranes. The results show that, after Con A has bound, rearrangements occur in the membrane that alter properties of the skeletal proteins. Additionally, redistribution of the skeletal proteins and the Con A receptor occurs in the lectin-agglutinated membranes.

Formononetin protects against concanavalin-A-induced autoimmune hepatitis in mice through its anti-apoptotic and anti-inflammatory properties

2021 ◽  
Vol 99 (2) ◽  
pp. 231-240
Author(s):  
Guangwei Liu ◽  
Wenxia Zhao ◽  
Jiameng Bai ◽  
Jianjiao Cui ◽  
Haowei Liang ◽  
...  
Keyword(s):  
Autoimmune Hepatitis ◽  
Concanavalin A ◽  
Nuclear Factor Kappa B ◽  
Caspase 3 ◽  
Receptor Protein ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Apoptotic Protein ◽  
Natural Herb ◽  
Dose Dependent

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that seriously threatens the health of humans globally. Formononetin (FMN) is a natural herb extract with multiple biological functions. In this study, an experimental model of AIH was established in mice through the use of concanavalin A (ConA). To investigate the effects of FMN on ConA-induced hepatitis, the mice were pretreated with 50 or 100 mg/kg body mass of FMN. The results show that FMN alleviated ConA-induced liver injury of mice in a dose-dependent manner. Moreover, pretreatment with FMN inhibited the apoptosis of hepatocytes in the ConA-treated mice through downregulating the expression of pro-apoptotic proteins (Bax, cleaved caspase 9, and cleaved caspase 3) and upregulating the expression of anti-apoptotic protein (Bcl-2). It was also found that the levels of proinflammatory cytokines were greatly reduced in the serum and liver tissues of mice pretreated with FMN. Further studies showed that FMN reduced the level of phosphorylated nuclear factor kappa B (p-NF-κB) p65 and enhanced the level of IκBα (inhibitor of NF-κB), suggesting that FMN inhibits the activation of the NF-κB signaling pathway. In addition, FMN inhibited activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Therefore, FMN could be a promising agent for the treatment of AIH.

scholarly journals Enhancement of desensitization of quisqualate-type glutamate receptor by the dissociative anaesthetic ketamine

1989 ◽  
Vol 141 (1) ◽  
pp. 73-86
Author(s):  
M. L. Ashford ◽  
P. Boden ◽  
R. L. Ramsey ◽  
P. N. Usherwood
Keyword(s):  
Glutamate Receptor ◽  
Dose Response ◽  
Concanavalin A ◽  
Rise Time ◽  
Voltage Dependence ◽  
Dependent Manner ◽  
Response Curves ◽  
Concomitant Reduction ◽  
The Right ◽  
Dose Dependent

Application of ketamine (10(−4)-10(−3)mol l-1) to locust retractor unguis muscle produced a reversible, dose-dependent reduction in neurally evoked twitches, and blocked agonist-induced contractions. With increasing ketamine concentration (5 × 10(−5)-10(−3) mol l-1), the amplitude of glutamate potentials was reduced and dose-response curves for ionophoresis of L-glutamate were shifted to the right, particularly after concanavalin A treatment. Ketamine (10(−4) mol l-1) enhanced the rate of desensitization to consecutive pulses of L-glutamate and this action was eliminated by concanavalin A. The amplitude of the excitatory postsynaptic current (EPSC) was reduced by ketamine (10(−5)-5 × 10(−4) mol l-1) in a dose-dependent manner but without a concomitant reduction in EPSC rise time. The decay phase of the EPSC was usually biphasic in the presence of ketamine (greater than 5 × 10(−5) mol l-1) but did not exhibit any voltage dependence. It is concluded that ketamine enhances desensitization and blocks the channel, particularly the closed form.

scholarly journals Thymoquinone Attenuates Immune Mediated Liver Injury Induced by Concanavalin A in Mice

2021 ◽  
Vol 30 (2) ◽  
pp. 50-57
Author(s):  
Halla A. Ahmad ◽  
Sarmed H. Kathem
Keyword(s):  
Liver Injury ◽  
Inflammatory Cytokines ◽  
Liver Damage ◽  
Concanavalin A ◽  
Liver Tissue ◽  
Tissue Homogenate ◽  
Control Group ◽  
Dependent Manner ◽  
Immune Mediated ◽  
Dose Dependent

Autoimmune hepatitis is an inflammatory disease and its incidence has been increasing. The features of hepatitis are the release of inflammatory cytokines, the elevation of AST and ALT, and hepatocyte apoptosis and necrosis. Concanavalin A considered as essential model represents the acute immune-mediated liver damage in rodents. Thymoquinone is well known herbal compound that exert hepatoprotective, anti-inflammatory, and antioxidant activity. In this study, we focus on the immunoregulatory and liver protective effect of thymoquinone in a mouse model of concanavalin A-induced liver injury. Twenty-four male mice were randomly divided into four groups each containing six animals: Negative control group, concanavalin A model group, thymoquinone 15mg/kg group, and thymoquinone 30mg/kg group. Blood was collected to detect the activities of alanine transaminase (ALT) and aspartate transaminase (AST) as well as liver tissue for the detection of tumor necrosis factor  levels, after 8 hours of concanavalin A injection. Injecting mice with concanavalin resulted in a dramatic increase in serum level of both ALT and AST which indicate severe liver tissue damage with a significant increase in inflammatory cytokines TNF alpha - and INF  levels, with a notable increase in NF-kB gene expression in mice liver tissue homogenate. Thymoquinone pretreatment revealed a dose-dependent increase in liver tissue protection. Conclusion: Thymoquinone has hepatoprotective and immune modulatory effects in concanavalin A induced immune mediated liver damage. Thymoquinone exerted its effect through attenuating NF and its downstream effectors TNF  and INF  in a dose dependent manner.

scholarly journals A New Immunosuppressive Pregnane Glycoside and Two Known Analogues from Epigynum cochinchinensis

2018 ◽  
Vol 13 (6) ◽  
pp. 1934578X1801300
Author(s):  
Yuting Shao ◽  
Yan Zhao ◽  
Hong Zhang ◽  
Mengjun Jiang ◽  
Afsar Khan ◽  
...  
Keyword(s):  
Concanavalin A ◽  
Soluble Fraction ◽  
Spectroscopic Techniques ◽  
Dependent Manner ◽  
Immunosuppressive Activity ◽  
Con A ◽  
Phytochemical Investigation ◽  
Pregnane Glycoside ◽  
Dose Dependent

Phytochemical investigation of the ethyl acetate soluble fraction from the leaves of Epigynum cochinchinensis led to the isolation of one new C21 pregnane glycoside, epigycoside C (1), along with two known analogues epigycoside A (2) and epigynoside G (3). Their structures were elucidated on the basis of extensive spectroscopic techniques. The in vitro immunosuppressive activity of compound 1 was evaluated against concanavalin A (Con A)- and lipopolysaccharides (LPS)-stimulated proliferation of mice splenocytes. Compound 1 displayed significant immunosuppressive activities in a dose-dependent manner.

scholarly journals Concanavalin A Protects Mice from a Lethal Inoculation of Intragastric Klebsiella pneumoniae and Reduces the Induced Liver Damage

2007 ◽  
Vol 51 (9) ◽  
pp. 3122-3130 ◽  
Author(s):  
Chih-Feng Kuo ◽  
Ya-Hui Wang ◽  
Huan-Yao Lei ◽  
Chiou-Huey Wang ◽  
Nina Tsao
Keyword(s):  
Klebsiella Pneumoniae ◽  
Concanavalin A ◽  
Blood Levels ◽  
Dependent Manner ◽  
Vitro Assay ◽  
Invasive Diseases ◽  
Dose Dependent ◽  
Liver Infection ◽  
Liver Tissues

ABSTRACT Intragastric inoculation of Klebsiella pneumoniae can cause invasive diseases, including necrosis of liver tissues and bacteremia. The effect of concanavalin A (ConA) on K. pneumoniae was tested. Pretreatment with ConA was able to protect mice from K. pneumoniae infection in an intragastric model. K. pneumoniae-induced mouse death and liver injury such as liver necrosis, as well as blood levels of aspartate aminotransferase and alanine aminotransferase, were inhibited in a dose-dependent manner by ConA. ConA administered intravenously as late as 24 h after K. pneumoniae inoculation was still protective. In an in vitro assay, ConA was able to bind K. pneumoniae cells directly and further agglutinate them but had no effect on their in vitro growth. Surveys of bacterial counts of ConA-treated mice revealed that the bacteria were eliminated effectively in both blood and liver tissues. Furthermore, the bactericidal activity of macrophages against K. pneumoniae was also enhanced in a dose-dependent manner by ConA in an in vitro culture. These data suggest that ConA is a potentially therapeutic agent for K. pneumoniae-induced liver infection.

scholarly journals The Influence of Lycopene, [6]-Gingerol, and Silymarin on the Apoptosis on U-118MG Glioblastoma Cells In Vitro Model

Nutrients ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 96 ◽  
Author(s):  
Justyna Czarnik-Kwaśniak ◽  
Konrad Kwaśniak ◽  
Paulina Kwasek ◽  
Elżbieta Świerzowska ◽  
Agata Strojewska ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Healthy Lifestyle ◽  
Annexin V ◽  
Dependent Manner ◽  
Glioblastoma Cells ◽  
Mitochondrial Potential ◽  
Vitro Model ◽  
Risk Of Cancer ◽  
Dose Dependent

Background: Lycopene, gingerol, and silymarin have a potential anticancer activity in many types of neoplasms. Healthy lifestyle and proper diet are associated with a reduced risk of cancer and other diseases. Increasingly, clinical research focuses on the mechanisms of action of natural compounds and their impact on the development of cancer. The aim of the present study was to determine the effect of lycopene, gingerol, and silymarin on apoptosis, mitochondrial potential and caspase-3/7 activity in the U118-MG cell line. Methods: Human glioblastoma cells were incubated with lycopene, [6]-gingerol, and silymarin for 24 and 48 h. Apoptosis was monitored using the Annexin V labelling, caspase-3/7 activity, and early hallmark of apoptosis were determined with mitochondrial membrane potential changes. Results: Our data showed a significant decrease in the viability glioblastoma cells U118-MG after 48 h treatment with lycopene, [6]-gingerol, and silymarin. Conclusions: Our data could confirm the stimulative effects of used compounds on apoptosis and changes in mitochondrial potential in a dose-dependent manner.

Effect of recombinant tumor necrosis factor-α on three-dimensional growth, morphology, and invasiveness of human glioblastoma cells in vitro

1993 ◽  
Vol 78 (6) ◽  
pp. 952-958 ◽  
Author(s):  
Koichi Iwasaki ◽  
Lisa R. Rogers ◽  
Gene H. Barnett ◽  
Melinda L. Estes ◽  
Barbara P. Barna
Keyword(s):  
Tumor Necrosis ◽  
Three Dimensional ◽  
Dependent Manner ◽  
Glioblastoma Cells ◽  
Human Glioblastoma ◽  
Tnf Α ◽  
Human Glioblastoma Cells ◽  
Dose Dependent ◽  
Necrosis Factor

✓ In order to investigate the antiproliferative and anti-invasive effects of tumor necrosis factor (TNF)-α on human glioblastoma cells, an in vitro three-dimensional (anchorage-independent) assay was performed using Matrigel, a mixture of extracellular matrix proteins. Four glioblastoma-derived cell lines, including one cloned line, were cultured in Matrigel with or without TNF-α. In the Matrigel containing TNF-α, three of the four cell lines, including the cloned line, showed significant growth inhibition in a dose-dependent manner. Dramatic three-dimensional morphological differences were observed between TNF-treated and untreated glioblastoma cells cultured in Matrigel. Untreated cells formed large and highly branched colonies throughout the gel. In contrast, the majority of TNF-treated cells demonstrated truncated branching processes and, at a high TNF-α dose, an increasing number of cells remained in relatively small spherical aggregates, their cell processes being significantly reduced. Quantitative invasion assay using a micro-Boyden chamber system confirmed that TNF-treated cells lost invasiveness in a dose-dependent manner. These results suggest that TNF-α exerts not only antiproliferative but also anti-invasive effects on human glioblastoma cells in vitro. It is believed that this is the first report showing the anti-invasive effect of TNF-α on tumor cells.

scholarly journals DDRE-04. THE COMBINED TREATMENT OF L-ASPARAGINASE AND 6-DIAZO-5-OXO-L-NORLEUCINE INHIBIT THE PROLIFERATION OF TEMOZOLOMIDE-SENSITIVE OR RESISTANT GLIOBLASTOMA CELLS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. i7-i7
Author(s):  
Shigeo Ohba ◽  
Yuichi Hirose
Keyword(s):  
Cancer Metabolism ◽  
Standard Treatment ◽  
Therapeutic Option ◽  
Combined Treatment ◽  
Recurrent Glioblastoma ◽  
Dependent Manner ◽  
Glioblastoma Cells ◽  
Single Drug ◽  
Dose Dependent ◽  
U87 Cells

Abstract Glioblastoma is one of the aggressive brain tumors with a 5-year survival rate of < 10%. The standard treatment is maximal safe resection, followed by radiation therapy and temozolomide (TMZ). Clinically, the resistance to TMZ is a big problem. Cancer cells have been revealed to show different metabolism from normal cells. The object of this study is to evaluate whether cancer metabolism, especially asparagine, could be a new target of treatment in primary and recurrent glioblastoma. Glioblastoma cells (U251 and U87) were treated with L-asparaginase and/or 6-diazo-5-oxo-L-norleucine (DON). L-asparaginase converts asparagine into aspartate and depletes asparagine. DON is a glutamine analog that inhibits several glutamine-utilizing enzymes, including asparagine synthetase. L-asparaginase or DON suppressed the proliferation of U251, and U87 cells in a dose-dependent manner. Combined treatment with these drugs had a synergistic antiproliferative effect in these cell lines. The effect was counteracted by exogenous asparagine. The combined treatment induced greater apoptosis and autophagy than did single-drug treatment. Several clones of TMZ-resistant U251 were obtained after long treatment of TMZ to U251. The expression of MSH6, one of the mismatch repair proteins, was suppressed in these resistant clones. The synergistic effect of L-asparaginase and DON was detected in these U251-derived TMZ-resistant clones. These results suggest that the combination of L-asparaginase and DON could be a new therapeutic option for patients with primary and recurrent glioblastoma.

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