Cannabisin G from Sinomenium acutum Induces Apoptosis in Human Glioblastoma Cells

2020 ◽  
Vol 12 (6) ◽  
pp. 823-828
Author(s):  
Dianbao Zhang ◽  
Chunhe Li ◽  
Bo Li ◽  
Yu Wang ◽  
Zaixing Chen ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Dependent Manner ◽  
Dapi Staining ◽  
Concentration Dependent Manner ◽  
Migration Assay ◽  
H Nmr ◽  
Sinomenium Acutum ◽  
Current Therapies ◽  
Human Gbm ◽  
First Time

Glioblastoma (GBM) is the most common and lethal primary malignant tumor in human central nervous system, current therapies depend on surgical resection, chemotherapy and radiotherapy. The poor prognosis drives us to discover more potential natural products. Cannabisin G is a lignanamide with different effects on different cancer cells, but its effects on GBM cells are still unclear. In this study, cannabisin G was isolated from dried stem of Sinomenium acutum (Thunb.) Rehd. et Wils. by solvent extraction and various chromatographic methods for the first time. It was characterized by 1H-NMR and 13C-NMR. The human GBM cell U87 and U251 were used to investigate the bioactivities of cannabisin G. By CCK-8 assay, cannabisin G was found to significantly inhibit cell viabilities in a concentration-dependent manner. The cell migration was also remarkably blocked by cannabisin G, which was determined by transwell migration assay. Further, apoptotic changes were observed in nucleus morphology upon the treatment with cannabisin G by DAPI staining. To explore the underling mechanisms, MAPKs phosphorylation was detected by western blotting and the activation of MAPKs was found to be involved in the inhibitory effect on GBM cells. In summary, cannabisin G isolated from Sinomenium acutum (Thunb.) Rehd. et Wils. for the first time, was found to induce apoptosis in GBM cells, partly through the activation of MAPKs.

scholarly journals Brassinolide Enhances the Level of Brassinosteroids, Protein, Pigments, and Monosaccharides in Wolffia arrhiza Treated with Brassinazole

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1311
Author(s):  
Magdalena Chmur ◽  
Andrzej Bajguz
Keyword(s):  
Plant Growth ◽  
Growth And Development ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Plant Growth And Development ◽  
Concentration Dependent Manner ◽  
Spectrophotometric Methods ◽  
Synthetic Inhibitor ◽  
Wolffia Arrhiza ◽  
First Time

Brassinolide (BL) represents brassinosteroids (BRs)—a group of phytohormones that are essential for plant growth and development. Brassinazole (Brz) is as a synthetic inhibitor of BRs’ biosynthesis. In the present study, the responses of Wolffia arrhiza to the treatment with BL, Brz, and the combination of BL with Brz were analyzed. The analysis of BRs and Brz was performed using LC-MS/MS. The photosynthetic pigments (chlorophylls, carotenes, and xanthophylls) levels were determined using HPLC, but protein and monosaccharides level using spectrophotometric methods. The obtained results indicated that BL and Brz influence W. arrhiza cultures in a concentration-dependent manner. The most stimulatory effects on the growth, level of BRs (BL, 24-epibrassinolide, 28-homobrassinolide, 28-norbrassinolide, catasterone, castasterone, 24-epicastasterone, typhasterol, and 6-deoxytyphasterol), and the content of pigments, protein, and monosaccharides, were observed in plants treated with 0.1 µM BL. Whereas the application of 1 µM and 10 µM Brz caused a significant decrease in duckweed weight and level of targeted compounds. Application of BL caused the mitigation of the Brz inhibitory effect and enhanced the BR level in duckweed treated with Brz. The level of BRs was reported for the first time in duckweed treated with BL and/or Brz.

Adrenomedullin inhibits angiotensin II-induced oxidative stress via Csk-mediated inhibition of Src activity

2007 ◽  
Vol 292 (4) ◽  
pp. H1714-H1721 ◽  
Author(s):  
Jing Liu ◽  
Tatsuo Shimosawa ◽  
Hiromitsu Matsui ◽  
Fanyin Meng ◽  
Scott C. Supowit ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Ros Production ◽  
Ang Ii ◽  
Concentration Dependent Manner ◽  
Cardiovascular Damage ◽  
Cgrp Receptor Antagonist ◽  
First Time

We have demonstrated that adrenomedullin (AM) protects against angiotensin II (ANG II)-induced cardiovascular damage through the attenuation of increased oxidative stress observed in AM-deficient mice. However, the mechanism(s) that underlie this activity remain unclear. To address this question, we investigated the effect of AM on ANG II-stimulated reactive oxygen species (ROS) production in cultured rat aortic vascular smooth muscle cells (VSMCs). ANG II markedly increased ROS production through activation of NADPH oxidase. This effect was significantly attenuated by AM in a concentration-dependent manner. This effect was mimicked by dibutyl-cAMP and blocked by pretreatment with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide hydrochloride (H-89), a protein kinase A inhibitor, and CGRP8–37, an AM/CGRP receptor antagonist. This inhibitory effect of AM was also lost following the expression of a constitutively active Src. Moreover, AM intersected ANG II signaling by inducing COOH-terminal Src kinase (Csk) activation that, in turn, inhibits Src activation. These data, for the first time, demonstrate that AM attenuates the ANG II-induced increase in ROS in VSMCs via activation of Csk, thereby inhibiting Src activity.

Cytotoxic Effects of Ferula Latisecta on Human Glioma U87 Cells

Drug Research ◽  
2019 ◽  
Vol 69 (12) ◽  
pp. 665-670 ◽  
Author(s):  
Mohammad Jalili-Nik ◽  
Hamed Sabri ◽  
Ehsan Zamiri ◽  
Mohammad Soukhtanloo ◽  
Mostafa Karimi Roshan ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Gelatin Zymography ◽  
Annexin V ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Induced Apoptosis ◽  
Natural Herb ◽  
First Time ◽  
U87 Cells

AbstractGlioblastoma multiforme (GBM) is the fatal type of astrocytic tumors with a survival rate of 12 months. The present study, for the first time, evaluated the cytotoxic impacts of Ferula latisecta (F. latisecta) hydroalcoholic extract on U87 GBM cell line. The MTT assay measured the cellular toxicity following 24- and 48 h treatment with various doses of F. latisecta (0–800 μg/mL). Apoptosis was evaluated by an Annexin V/propidium iodide (PI) staining 24 h after treatment by F. latisecta. Moreover, to determine the cellular metastasis of U87 cells, we used a gelatin zymography assay (matrix metalloproteinase [MMP]-2/-9 enzymatic activity). The outcomes showed that F. latisecta mitigated the viability of U87 cells in a concentration- and time-dependent manner with IC50 values of 145.3 and 192.3 μg/mL obtained for 24- and 48 h treatments, respectively. F. latisecta induced apoptosis in a concentration-dependent manner after 24 h. Also, MMP-9 activity was significantly decreased following 24 h after treatment concentration-dependently with no change in MMP-2 enzymatic activity. This study showed that F. latisecta induced cytotoxicity and apoptosis, and mitigated metastasis of U87 GBM cells. Hence, F. latisecta could be beneficial as a promising natural herb against GBM after further studies.

Adenosine A1 receptor-mediated inhibition of vasopressin action in inner medullary collecting duct

1994 ◽  
Vol 266 (5) ◽  
pp. F791-F796 ◽  
Author(s):  
R. M. Edwards ◽  
W. S. Spielman
Keyword(s):  
Receptor Agonist ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Camp Accumulation ◽  
Concentration Dependent Manner ◽  
Cgs 21680 ◽  
Camp Generation ◽  
A1 Receptor

We examined the effects of adenosine and adenosine analogues on arginine vasopressin (AVP)-induced increases in osmotic water permeability (Pf; micron/s) and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in rat inner medullary collecting ducts (IMCDs). When added to the bath, the A1 receptor agonist N6-cyclohexyladenosine (CHA) produced a rapid and reversible inhibition of AVP-stimulated (10 pM) Pf (1,781 +/- 195 to 314 +/- 85 microns/s at 0.3 microM CHA; n = 9). The inhibitory effect of CHA was concentration dependent, with a 50% inhibitory concentration of 10 nM. The effect of CHA was inhibited by prior exposure of IMCDs to the A1 receptor antagonist 1,3-dipropylxanthine-8-cyclopentylxanthine (DP-CPX; 1 microM) or by preincubation with pertussis toxin. CHA had no effect on cAMP-induced increases in Pf. In addition to CHA, adenosine and the nonselective agonist 5'-(N-ethylcarboxamido)-adenosine (NECA) inhibited AVP-dependent Pf by > or = 70%, whereas the A2 receptor agonist CGS-21680 had no effect. Luminal adenosine (0.1 mM) had no effect on basal or AVP-stimulated Pf. CHA, NECA, and adenosine but not CGS-21680 inhibited AVP-stimulated cAMP accumulation in a concentration-dependent manner (50% inhibitory concentrations 0.1–300 nM). The inhibitory effect of CHA on AVP-stimulated cAMP accumulation was attenuated by DPCPX. We conclude that adenosine, acting at the basolateral membrane, inhibits AVP action in the IMCD via interaction with A1 receptors. The inhibition occurs proximal to cAMP generation and likely involves an inhibitory G protein.

Fibrinogen binding to the integrin αIIbβ3 modulates store-mediated calcium entry in human platelets

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2648-2656 ◽  
Author(s):  
Juan A. Rosado ◽  
Else M. Y. Meijer ◽  
Karly Hamulyak ◽  
Irena Novakova ◽  
Johan W. M. Heemskerk ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Polymerization ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Integrin Αiibβ3 ◽  
Fibrinogen Binding

Abstract Effects of the occupation of integrin αIIbβ3 by fibrinogen on Ca++signaling in fura-2–loaded human platelets were investigated. Adding fibrinogen to washed platelet suspensions inhibited increases in cytosolic [Ca++] concentrations ([Ca++]i) evoked by adenosine diphosphate (ADP) and thrombin in a concentration-dependent manner in the presence of external Ca++ but not in the absence of external Ca++ or in the presence of the nonselective cation channel blocker SKF96365, indicating selective inhibition of Ca++entry. Fibrinogen also inhibited store-mediated Ca++ entry (SMCE) activated after Ca++ store depletion using thapsigargin. The inhibitory effect of fibrinogen was reversed if fibrinogen binding to αIIbβ3 was blocked using RDGS or abciximab and was absent in platelets from patients homozygous for Glanzmann thrombasthenia. Fibrinogen was without effect on SMCE once activated. Activation of SMCE in platelets occurs through conformational coupling between the intracellular stores and the plasma membrane and requires remodeling of the actin cytoskeleton. Fibrinogen inhibited actin polymerization evoked by ADP or thapsigargin in control cells and in cells loaded with the Ca++ chelator dimethyl BAPTA. It also inhibited the translocation of the tyrosine kinase p60src to the cytoskeleton. These results indicate that the binding of fibrinogen to integrin αIIbβ3 inhibits the activation of SMCE in platelets by a mechanism that may involve modulation of the reorganization of the actin cytoskeleton and the cytoskeletal association of p60src. This action may be important in intrinsic negative feedback to prevent the further activation of platelets subjected to low-level stimuli in vivo.

Thrombin activatable fibrinolysis inhibitor (TAFI) affects fibrinolysis in a plasminogen activator concentration-dependent manner

2004 ◽  
Vol 91 (03) ◽  
pp. 473-479 ◽  
Author(s):  
Ana Guimarães ◽  
Dingeman Rijken
Keyword(s):  
Plasminogen Activator ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Retardation Factor ◽  
Clot Lysis ◽  
Dependent Manner ◽  
Plasma Clot ◽  
Concentration Dependent Manner ◽  
Plasmin Inhibitor

SummaryTAFIa was shown to attenuate fibrinolysis. In our in vitro study, we investigated how the inhibitory effect of TAFIa depended on the type and concentration of the plasminogen activator (PA). We measured PA-mediated lysis times of plasma clots under conditions of maximal TAFI activation by thrombin-thrombomodulin in the absence and presence of potato carboxypeptidase inhibitor. Seven different PAs were compared comprising both tPA-related (tPA, TNK-tPA, DSPA), bacterial PA-related (staphylokinase and APSAC) and urokinase-related (tcu-PA and k2tu-PA) PAs. The lysis times and the retardation factor were plotted against the PA concentration. The retardation factor plots were bell-shaped. At low PA concentrations, the retardation factor was low, probably due to the limited stability of TAFIa. At intermediate PA concentrations the retardation factor was maximal (3-6 depending on the PA), with TNK-tPA, APSAC and DSPA exhibiting the strongest effect. At high PA concentrations, the retardation factor was again low, possibly due to inactivation of TAFIa by plasmin or to a complete conversion of glu-plasminogen into lys-plasminogen. Using individual plasmas with a reduced plasmin inhibitor activity (plasmin inhibitor Enschede) the bell-shaped curve of the retardation factor shifted towards lower tPA and DSPA concentrations, but the height did not decrease. In conclusion, TAFIa delays the lysis of plasma clots mediated by all the plasminogen activators tested. This delay is dependent on the type and concentration of the plasminogen activator, but not on the fibrin specificity of the plasminogen activator. Furthermore, plasmin inhibitor does not play a significant role in the inhibition of plasma clot lysis by TAFI.

scholarly journals Inhibition of Cytochrome P450 (CYP450) Isoforms by Isoniazid: Potent Inhibition of CYP2C19 and CYP3A

2001 ◽  
Vol 45 (2) ◽  
pp. 382-392 ◽  
Author(s):  
Zeruesenay Desta ◽  
Nadia V. Soukhova ◽  
David A. Flockhart
Keyword(s):  
Cytochrome P450 ◽  
Liver Microsomes ◽  
Cost Effective ◽  
Competitive Inhibitor ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Specific Substrate ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
The Mean

ABSTRACT Isoniazid (INH) remains the most safe and cost-effective drug for the treatment and prophylaxis of tuberculosis. The use of INH has increased over the past years, largely as a result of the coepidemic of human immunodeficiency virus infection. It is frequently given chronically to critically ill patients who are coprescribed multiple medications. The ability of INH to elevate the concentrations in plasma and/or toxicity of coadministered drugs, including those of narrow therapeutic range (e.g., phenytoin), has been documented in humans, but the mechanisms involved are not well understood. Using human liver microsomes (HLMs), we tested the inhibitory effect of INH on the activity of common drug-metabolizing human cytochrome P450 (CYP450) isoforms using isoform-specific substrate probe reactions. Incubation experiments were performed at a single concentration of each substrate probe at its Km value with a range of INH concentrations. CYP2C19 and CYP3A were inhibited potently by INH in a concentration-dependent manner. At 50 μM INH (∼6.86 μg/ml), the activities of these isoforms decreased by ∼40%. INH did not show significant inhibition (<10% at 50 μM) of other isoforms (CYP2C9, CYP1A2, and CYP2D6). To accurately estimate the inhibition constants (Ki values) for each isoform, four concentrations of INH were incubated across a range of five concentrations of specific substrate probes. The meanKi values (± standard deviation) for the inhibition of CYP2C19 by INH in HLMs and recombinant human CYP2C19 were 25.4 ± 6.2 and 13 ± 2.4 μM, respectively. INH showed potent noncompetitive inhibition of CYP3A (Ki = 51.8 ± 2.5 to 75.9 ± 7.8 μM, depending on the substrate used). INH was a weak noncompetitive inhibitor of CYP2E1 (Ki = 110 ± 33 μM) and a competitive inhibitor of CYP2D6 (Ki = 126 ± 23 μM), but the mean Ki values for the inhibition of CYP2C9 and CYP1A2 were above 500 μM. Inhibition of one or both CYP2C19 and CYP3A isoforms is the likely mechanism by which INH slows the elimination of coadministered drugs, including phenytoin, carbamazepine, diazepam, triazolam, and primidone. Slow acetylators of INH may be at greater risk for adverse drug interactions, as the degree of inhibition was concentration dependent. These data provide a rational basis for understanding drug interaction with INH and predict that other drugs metabolized by these two enzymes may also interact.

scholarly journals Inhibition of HepG-2 Cells (Liver Cancer Cell Line) Viability by 3-Hydroxypyridine-2-Carboxaldehyde N(4)-Methylthiosemicarbazone

2021 ◽  
Vol 8 (2) ◽  
pp. 88-97
Author(s):  
Edrees Khan Rahmatzada ◽  
Prof. Paras Nath Yadav ◽  
Dr. Yuba Raj Pokharel
Keyword(s):  
Cancer Cell Line ◽  
Mapk Signaling ◽  
In Vivo Model ◽  
Dependent Manner ◽  
Dapi Staining ◽  
Concentration Dependent Manner ◽  
Anticancer Effects ◽  
Ic50 Value ◽  
Colony Number

Thiosemicarbazone have the antiviral, antibacterial, antifungal, and anticancer effects. 3-OH-Me-TSC inhibited the cell viability of HepG-2 cells by CV assay in a concentration dependent manner (control, 1μM, 3μM, 10μM, 30μM, and 100μM) with IC50 value of 9.587622μM. Further colony formation assay demonstrated that 3-OH-Me-TSC inhibits colony number and size of HepG-2. Wound healing assay exhibited that 3-OH-Me-TSC inhibit the migration of HepG-2 cells. DAPI staining showed that 3-OH-Me-TSC inhibited proliferation of HepG-2 cells in 30μM and 100μM concentrations respectively. 3-OH-Me-TSC inhibited VEGF, p38 alpha, C-JUN, BECN-1, ERK, NF-KB, in HepG-2 cells. We found that 3-OH-Me-TSC inhibit proliferation of HepG-2 cells by inhibiting MAPK signaling pathway, 3-OH-Me-TSC can be developed as future chemotherapeutic agent for treatment of hepatocellular carcinoma after the evaluation of this compounds in more cancer cells an in vivo model.

Small Molecule Constituents of Periplaneta americana and Their IL-6 Inhibitory Activities

2021 ◽  
Vol 16 (9) ◽  
pp. 1934578X2110331
Author(s):  
Hua-Sheng Zhang ◽  
Yong-Ming Yan ◽  
Dai-Wei Wang ◽  
Qing Lv ◽  
Yong-Xian Cheng ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Periplaneta Americana ◽  
Ethanol Extract ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Chemical Methods ◽  
Concentration Dependent Manner ◽  
Inhibitory Activities ◽  
First Time

Two new glycosides, periplanosides A (1) and B (2), 3 compounds reported from a natural source for the first time (3 − 5), and 6 known compounds 6 − 11 were isolated from the ethanol extract of Periplaneta americana (Linnaeus). Their structures, including absolute configurations, were unambiguously identified by comprehensive spectroscopic and chemical methods. Compound 3 is a racemate whose enantiomers were purified by chiral high-performance liquid chromatography . The biological evaluation results showed that compound 7 (0 − 20 μM) did not affect the viability of RAW264.7 cells and could effectively inhibit the production of interleukin-6 stimulated by lipopolysaccharide in a concentration-dependent manner, indicating the potential to develop novel agents against inflammation-related diseases.

Betulinic acid induces apoptosis of gallbladder cancer cells via repressing SCD1

2020 ◽  
Vol 52 (2) ◽  
pp. 200-206 ◽  
Author(s):  
Hongfei Wang ◽  
Fangxiao Dong ◽  
Ye Wang ◽  
Xu’an Wang ◽  
Defei Hong ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Betulinic Acid ◽  
Polymerase Chain Reaction Analysis ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Concentration Dependent Manner ◽  
Polymerase Chain ◽  
Induced Apoptosis ◽  
Scd1 Expression

Abstract Gallbladder cancer (GBC) is the most common and aggressive malignancy of the biliary tract. Betulinic acid (BetA) has been reported to have anti-inflammatory and antitumor effects; however, the effect of BetA on GBC is still unknown. In this study, we investigated the effect of BetA on five GBC cell lines and found that BetA significantly inhibited the proliferation of NOZ cells but had little inhibitory effect on other GBC cells. BetA disturbed mitochondrial membrane potential and induced apoptosis in NOZ cells. Real-time polymerase chain reaction analysis revealed that stearoyl-coenzyme A desaturase 1 (SCD1) was highly expressed in NOZ cells but low expressed in other GBC cells. BetA inhibited SCD1 expression in a concentration-dependent manner in NOZ cells. Downregulation of SCD1 expression by RNA interference inhibited the proliferation of NOZ cells and induced cell apoptosis. Moreover, BetA inhibited the growth of xenografted tumors and suppressed SCD1 expression in nude mice. Thus, our results showed that BetA induced apoptosis through repressing SCD1 expression in GBC, suggesting that BetA might be an effective agent for the treatment of patients with GBC that highly expresses SCD1.

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