scholarly journals N-Alkyl-Substituted Isatins Enhance P2X7 Receptor-Induced Interleukin-1βRelease from Murine Macrophages

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ronald Sluyter ◽  
Kara L. Vine
Keyword(s):  
P2x7 Receptor ◽  
Colorimetric Assay ◽  
Dependent Manner ◽  
Dye Uptake ◽  
Anticancer Activities ◽  
Concentration Dependent Manner ◽  
Parent Molecule ◽  
Murine Macrophages ◽  
Ldh Release ◽  
Isatin Derivatives

Extracellular adenosine 5′-triphosphate (ATP) activates the P2X7 receptor channel to induce the rapid release of the proinflammatory cytokine, interleukin- (IL-) 1β, from macrophages. Microtubule rearrangements are thought to be involved in this process. Some isatin derivatives alter microtubules and display anticancer activities. The current study investigated the effect of isatin and seven structurally diverse isatin derivatives on P2X7-mediated IL-1βrelease from murine J774 macrophages. ATP-induced IL-1βand lactate dehydrogenase (LDH) release were assessed by specific colorimetric assays. P2X7 activity was determined by flow cytometric measurements of ATP-induced cation dye uptake. Cytotoxicity of isatin derivatives was determined using a tetrazolium-based colorimetric assay. ATP caused rapid IL-1βrelease in a concentration-dependent manner, and this process was completely impaired by the P2X7 antagonist, AZ10606120. In contrast, 5,7-dibromo-N-(p-methoxybenzyl)isatin (NAI) and 3-{4-[5,7-dibromo-1-(4-methoxybenzyl)-2-oxoindolin-3-ylidenamino]phenyl}propanoic acid (NAI-imine) enhanced P2X7-induced IL-1βrelease by twofold compared to that of isatin and the parent molecule, 5,7-dibromoisatin. NAI and NAI-imine had minimal effect on P2X7-induced dye uptake and LDH release. In contrast, 24-hour incubation with NAI and NAI-imine (in the absence of exogenous ATP) induced macrophage death in a concentration-dependent manner. In conclusion, this study demonstrates thatN-alkyl-substituted isatins enhance P2X7 receptor-induced IL-1βrelease from murine macrophages. Thus, in addition to direct anticancer effects, these compounds may also impact inflammatory and immune cells within the tumor microenvironment.

scholarly journals In vitroAnticancer Evaluation of Saponins Obtained From Spirulina platensis on MDA, HepG2, and MCF7 Cell Lines

2019 ◽  
Vol 3 (4) ◽  
pp. 25-32
Author(s):  
Mahboobeh Akbarizare ◽  
Hamideh Ofoghi ◽  
Mahnaz Hadizadeh
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
Spirulina Platensis ◽  
Dependent Manner ◽  
Cellular Viability ◽  
Breast Cancers ◽  
Anticancer Activities ◽  
Concentration Dependent Manner ◽  
Photosynthetic Microorganism ◽  
Mcf 7

Introduction: Microalgae are known for their bioactive compounds with potential applications as antimicrobial, antiaging, and anticancer activities. Spirulina platensis (S. platensis) is a filamentous and photosynthetic microorganism that has 25 kinds of vitamins and minerals that contain many compounds with biotic activity such as alkaloids, phenolic compounds, terpenoids, and saponins. Saponins are mainly present in plants; while there are few studies about their role in microalgae. This study aims to investigate the anticancer potential of extracted saponins from S. platensis. Methods: Saponins were extracted; using distilled water and n-butanol. The total extracted saponin was dried and weighed. The cellular viability of HepG2, MCF-7, and MDA- MB-123 cell lines was evaluated; using MTT assay after 24 h treatment with 0.02-2 mg/ ml of saponins extracted from S. platensis. Morphology of cell lines was evaluated by invert microscopy. Results: Total saponin extracted from S. platensis was estimated at 28±0.0005 mg/g dry wt. Thin-layer chromatography profiles showed four bands for saponins with Rf values of 0.44, 0.48, 0.50, and 0.55. The cytotoxic activity after 24 h treatment with 0.02-2 mg/ml of saponins was a concentration-dependent manner. The highest toxicity of saponins with IC50=0.22 mg/ml was observed in MDA-MB-123 cells. In HepG2 and MCF-7 cells IC50 value was obtained in 0.35 mg/ml and 0.4 mg/ml, respectively. Conclusions: This is the first report to evaluate the anticancer effects of saponins from S. platensis in liver and breast cancers. The result showed that saponins from Spirulina decrease cancer cellular viability. Therefore, these compounds can be a candidate for anticancer agents.

Hesperidin Prevents High Glucose-Induced Damage of Retinal Pigment Epithelial Cells

Planta Medica ◽  
2018 ◽  
Vol 84 (14) ◽  
pp. 1030-1037 ◽  
Author(s):  
Wayne Liu ◽  
Shorong-Shii Liou ◽  
Tang-Yao Hong ◽  
I-Min Liu
Keyword(s):  
High Glucose ◽  
Retinal Pigment Epithelial ◽  
Colorimetric Assay ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Antioxidant Enzyme Activities ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Rpe Cells ◽  
Pigment Epithelial

AbstractThe present study aimed to determine whether hesperidin, a plant-based active flavanone found in citrus fruits, can prevent high glucose-induced retinal pigment epithelial (RPE) cell impairment. Cultured human RPE cells (ARPE-19) were exposed to a normal glucose concentration (5.5 mM) for 4 d and then soaked in either normal (5.5 mM) or high (33.3 mM) concentrations of D-glucose with or without different concentrations of hesperidin (10, 20, or 40 µM) for another 48 h. The survival rates of the cells were measured using a 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction assay. With the help of a fluorescent probe, the intracellular production of reactive oxygen species (ROS) was evaluated. Colorimetric assay kits were used to assess the antioxidant enzyme activities, and western blotting was used to measure the expression of apoptosis-related protein. Hesperidin was effective in inhibiting high glucose-induced ROS production, preventing loss of cell viability, and promoting the endogenous antioxidant defense components, including glutathione peroxidase, superoxide dismutase, catalase, and glutathione, in a concentration-dependent manner. Furthermore, high glucose triggered cell apoptosis via the upregulation of caspase-9/3, enhancement of cytochrome c release into the cytosol, and subsequent interruption of the Bax/Bcl-2 balance. These detrimental effects were ameliorated by hesperidin in a concentration-dependent manner. We conclude that through the scavenging of ROS and modulation of the mitochondria-mediated apoptotic pathway, hesperidin may protect RPE cells from high glucose-induced injury and thus may be a candidate in preventing the visual impairment caused by diabetic retinopathy.

Exogenous NO inhibits basal NO release from vascular endothelium in vitro and in vivo

1996 ◽  
Vol 271 (5) ◽  
pp. H2045-H2051 ◽  
Author(s):  
X. L. Ma ◽  
B. L. Lopez ◽  
T. A. Christopher ◽  
D. S. Birenbaum ◽  
J. Vinten-Johansen
Keyword(s):  
In Vivo Studies ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
No Donor ◽  
Parent Molecule ◽  
Arterial Blood ◽  
No Release ◽  
Basal Release

This study tested the hypothesis that exogenous nitric oxide (NO) inhibits basal release of NO in isolated rat aortic rings and in vivo. Thoracic aortic rings were suspended in organ chambers with Krebs-Henseleit solution. In untreated rings, the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) markedly increased basal vascular tone by 34.6 +/- 5.2% of maximal force produced by 100 nM thromboxane A2 mimetic U-46619, indicating a basal release of NO. Other rings were pretreated with the exogenous NO donor S-nitroso-N-acetylpenicillamine (SNAP) for 20 min and then washed free of drug. In these rings, L-NAME-induced vasoconstriction was significantly attenuated in a concentration-dependent manner (from 34.6 +/- 5.2 to 25.7 +/- 2.9% at SNAP = 0.5 microM, 15.2 +/- 3.1% at 1 microM, and 11.9 +/- 2.5% at 5 microM), while having no effect on NO-independent phenylephrine-induced vasoconstriction (35.4 +/- 4.7 untreated vs. 41.3 +/- 4.3% SNAP pretreated, not significant). In addition, the nonnitrosylated parent molecule of SNAP, acetylpenicillamine, had no effect on the vasoconstriction induced by L-NAME. In the in vivo studies in anesthetized rats, L-NAME caused significant hypertensive responses (34 +/- 4-mmHg increase in mean arterial blood pressure). Subvasoactive doses of SNAP attenuated these hypertensive responses in a dose-dependent manner (20 +/- 3-mmHg increase with 10 micrograms/kg SNAP pretreatment and 16 +/- 4-mmHg increase with 20 micrograms/kg SNAP pretreatment), but any dose of acetylpenicillamine studied had no effect. Coadministration of superoxide dismutase and SNAP significantly potentiated the inhibitory effect of the NO donor on vasocontraction responses to L-NAME. Furthermore, SNAP did not attenuate the hypertensive responses to phenylephrine. These results indicate that exogenous NO significantly inhibits basal NO release both in vitro and in vivo, suggesting that NO plays an important negative-feedback regulatory role under physiological conditions.

scholarly journals Anticancer Activity of 2-O-caffeoyl Alphitolic Acid Extracted from the Lichen, Usnea barbata 2017-KL-10

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3937
Author(s):  
Hae-Jung Chae ◽  
Geum-Jin Kim ◽  
Barsha Deshar ◽  
Hyun-Jin Kim ◽  
Min-Ji Shin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Biological Activities ◽  
Biological Effects ◽  
Cancer Cell Line ◽  
Colorectal Cancer Cell Line ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Concentration Dependent Manner ◽  
Mortality And Morbidity

Colorectal cancer is one of the life-threatening ailments causing high mortality and morbidity worldwide. Despite the innovation in medical genetics, the prognosis for metastatic colorectal cancer in patients remains unsatisfactory. Recently, lichens have attracted the attention of researchers in the search for targets to fight against cancer. Lichens are considered mines of thousands of metabolites. Researchers have reported that lichen-derived metabolites demonstrated biological effects, such as anticancer, antiviral, anti-inflammatory, antibacterial, analgesic, antipyretic, antiproliferative, and cytotoxic, on various cell lines. However, the exploration of the biological activities of lichens’ metabolites is limited. Thus, the main objective of our study was to evaluate the anticancer effect of secondary metabolites isolated from lichen (Usnea barbata 2017-KL-10) on the human colorectal cancer cell line HCT116. In this study, 2OCAA exhibited concentration-dependent anticancer activities by suppressing antiapoptotic genes, such as MCL-1, and inducing apoptotic genes, such as BAX, TP53, and CDKN1A(p21). Moreover, 2OCAA inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that 2OCAA is a better therapeutic candidate for colorectal cancer.

Comparative cardioprotective effects of cromakalim and diltiazem in ischemic hypertrophied rat hearts

1996 ◽  
Vol 270 (1) ◽  
pp. H174-H182
Author(s):  
G. J. Grover ◽  
S. Dzwonczyk ◽  
T. M. Monticello
Keyword(s):  
Cardiac Hypertrophy ◽  
Contractile Function ◽  
Heart Weight ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Concentration Dependent Manner ◽  
Rat Hearts ◽  
Cardioprotective Effects ◽  
Ldh Release ◽  
Wistar Kyoto

Previous studies have indicated that alterations in cardiac ATP-sensitive potassium channels (KATP) can occur with cardiac hypertrophy. The goal of this study was to determine the effect of cardiac hypertrophy in spontaneously hypertensive rats (SHR) on the response to the cardioprotective agents diltiazem and cromakalim. Isolated rat hearts from 14-wk-old SHR, normotensive heterozygote Wistar-Kyoto (WKY), and Sprague-Dawley (SD) strains were subjected to 25 min of global ischemia and 30 min of reperfusion in the presence of vehicle (3-30 microM cromakalim or 0.1-1.0 microM diltiazem). SHR had heart weight-to-body weight ratios 40-50% greater than age-matched SD or WKY. Both diltiazem and cromakalim increased reperfusion contractile function in a concentration-dependent manner in SD rats as previously reported. Cromakalim and diltiazem caused similar improvements in reperfusion function in WKY rats and SHR. Cumulative lactate dehydrogenase (LDH) release during reperfusion was similar for vehicle-treated SD, WKY, or SHR hearts. LDH release was significantly attenuated by cromakalim and dilitiazem at all concentrations tested in SD and WKY hearts, whereas LDH release was not attenuated in SHR hearts by any concentration of cromakalim or diltiazem tested. Morphological assessment of hearts by light microscopy indicated that the severity and distribution of myocardial lesions were not affected by cromakalim in SHR hearts, compared with vehicle-treated SHR, supporting the LDH data. These results suggest that in SHR hearts, cromakalim and dilitiazan may exert much of their cardioprotective effects on the population of myocytes that are not irreversibly damaged.

8-Hydroxy-2-(1H-1,2,3-triazol-1-yl)-1,4-naphtoquinone derivatives inhibited P2X7 Receptor-Induced dye uptake into murine Macrophages

2019 ◽  
Vol 27 (8) ◽  
pp. 1449-1455 ◽  
Author(s):  
P.A.F. Pacheco ◽  
R.M.S. Galvão ◽  
A.F.M. Faria ◽  
N.l. Von Ranke ◽  
M.S. Rangel ◽  
...  
Keyword(s):  
P2x7 Receptor ◽  
Dye Uptake ◽  
Murine Macrophages

scholarly journals New Properties and Mitochondrial Targets of Polyphenol Agrimoniin as a Natural Anticancer and Preventive Agent

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2089
Author(s):  
Tatiana A. Fedotcheva ◽  
Olga P. Sheichenko ◽  
Nadezhda I. Fedotcheva
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Concentration Dependent Manner ◽  
Succinate Oxidation ◽  
Mitochondrial Functions

Agrimoniin is a polyphenol from the group of tannins with antioxidant and anticancer activities. It is assumed that the anticancer action of agrimoniin is associated with the activation of mitochondria-dependent apoptosis, but its mitochondrial targets have not been estimated. We examined the direct influence of agrimoniin on different mitochondrial functions, including the induction of the mitochondrial permeability transition pore (MPTP) as the primary mechanism of mitochondria-dependent apoptosis. Agrimoniin was isolated from Agrimonia pilosa Ledeb by multistep purification. The content of agrimoniin in the resulting substance reached 80%, as determined by NMR spectroscopy. The cytotoxic effect of purified agrimoniin was confirmed on the cultures of K562 and HeLa cancer cells by the MTT assay. When tested on isolated rat liver mitochondria, agrimoniin at a low concentration (10 µM) induced the low-amplitude swelling, which was inhibited by the MPTP inhibitors ADP and cyclosporine A, activated the opening of MPTP by calcium ions and stimulated the respiration supported by succinate oxidation. Also, agrimoniin reduced the electron acceptor DCPIP in a concentration-dependent manner and chelated iron ions. Owing to all these properties, agrimoniin can stimulate apoptosis or activate mitochondrial functions, which can be helpful in the prevention and elimination of stagnant pathological states.

scholarly journals Semi-Synthesis and In Vitro Anti-Cancer Evaluation of Magnolol Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4302
Author(s):  
Xiao-Long Sun ◽  
Mei-Lin Zhu ◽  
Yi-Qun Dai ◽  
Hong-Mei Li ◽  
Bo-Han Li ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
Biological Activities ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Antitumor Effects ◽  
Concentration Dependent Manner ◽  
Human Cancer Cell Lines

Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC50 values ranging from 20.43 to 28.27 μM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.

The Anti-Atherogenic Properties of Sesamin are Mediated via Improved Macrophage Cholesterol Efflux Through PPARγ1-LXRα and MAPK Signaling

2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro
Keyword(s):  
Cholesterol Efflux ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Mapk Signaling ◽  
Luciferase Reporter ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Macrophage Cholesterol Efflux

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.

Neutrophil Elastase Potentiates Cathepsin G-lnduced Platelet Activation

1992 ◽  
Vol 68 (05) ◽  
pp. 570-576 ◽  
Author(s):  
Mary A Selak
Keyword(s):  
Neutrophil Elastase ◽  
Cell Activation ◽  
Thromboxane A2 ◽  
Creatine Phosphate ◽  
Dense Granule ◽  
Cathepsin G ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Low Concentrations ◽  
High Concentrations

SummaryWe have previously demonstrated that human neutrophil cathepsin G is a strong platelet agonist that binds to a specific receptor. This work describes the effect of neutrophil elastase on cathepsin G-induced platelet responses. While platelets were not activated by high concentrations of neutrophil elastase by itself, elastase enhanced aggregation, secretion and calcium mobilization induced by low concentrations of cathepsin G. Platelet aggregation and secretion were potentiated in a concentration-dependent manner by neutrophil elastase with maximal responses observable at 200 nM. Enhancement was observed when elastase was preincubated with platelets for time intervals of 10–60 s prior to addition of a low concentration of cathepsin G and required catalytically-active elastase since phenylmethanesulphonyl fluoride-inhibited enzyme failed to potentiate cell activation. Neutrophil elastase potentiation of platelet responses induced by low concentrations of cathepsin G was markedly inhibited by creatine phosphate/creatine phosphokinase and/or indomethacin, indicating that the synergism between elastase and cathepsin G required the participation of ADP and thromboxane A2. On the other hand, platelet responses were not attenuated by the PAF antagonist BN 52021, signifying that PAF-acether did not play a role in elastase potentiation. At higher concentrations porcine pancreatic elastase exhibits similar effects to neutrophil elastase, demonstrating that the effect of elastase was not unique to the neutrophil protease. While neutrophil elastase failed to alter the ability of cathepsin G to hydrolyze a synthetic chromogenic substrate, preincubation of platelets with elastase increased the apparent affinity of cathepsin G binding to platelets. In contrast to their effect on cathepsin G-induced platelet responses, neither neutrophil nor pancreatic elasatse potentiated aggregation or dense granule release initiated by ADP, PAF-acether, arachidonic acid or U46619, a thromboxane A2 mimetic. Moreover, unlike its effect on cathepsin G, neutrophil elastase inhibited thrombin-induced responses. The current observations demonstrate that elastase can potentiate platelet responses mediated by low concentrations of cathepsin G, suggesting that both enzymes may function synergistically to activate platelets under conditions where neutrophil degranulation occurs.

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