scholarly journals Melatonin Modulation of Radiation and Chemotherapeutics-induced Changes on Differentiation of Breast Fibroblasts

2019 ◽  
Vol 20 (16) ◽  
pp. 3935 ◽  
Author(s):  
Alicia González-González ◽  
Enrique García Nieto ◽  
Alicia González ◽  
Cristina Sánchez-Fernández ◽  
Carolina Alonso-González ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Aromatase Activity ◽  
Proliferation And Differentiation ◽  
Cox 2 ◽  
Regulatory Effects ◽  
Factor Α ◽  
Induced Changes ◽  
Pparγ Expression ◽  
Cox 1 ◽  
Breast Fibroblasts

Melatonin exerts oncostatic actions and sensitizes tumor cells to chemotherapeutics or radiation. In our study, we investigated the effects of docetaxel, vinorelbine, and radiation on human breast fibroblasts and its modulation by melatonin. Docetaxel or vinorelbine inhibits proliferation and stimulates the differentiation of breast preadipocytes, by increasing C/EBPα and PPARγ expression and by downregulating tumor necrosis factor α (TNFα), interleukin 6 (IL-6), and IL-11 expression. Radiation inhibits both proliferation and differentiation through the downregulation of C/EBPα and PPARγ and by stimulating TNFα expression. In addition, docetaxel and radiation decrease aromatase activity and expression by decreasing aromatase promoter II and cyclooxygenases 1 and 2 (COX-1 and COX-2) expression. Melatonin potentiates the stimulatory effect of docetaxel and vinorelbine on differentiation and their inhibitory effects on aromatase activity and expression, by increasing the stimulatory effect on C/EBPα and PPARγ expression and the downregulation of antiadipogenic cytokines and COX expression. Melatonin also counteracts the inhibitory effect of radiation on differentiation of preadipocytes, by increasing C/EBPα and PPARγ expression and by decreasing TNFα expression. Melatonin also potentiates the inhibitory effect exerted by radiation on aromatase activity and expression by increasing the downregulation of promoter II, and COX-1 and COX-2 expression. Our findings suggest that melatonin modulates regulatory effects induced by chemotherapeutic drugs or radiation on preadipocytes, which makes it a promising adjuvant for chemotherapy and radiotherapy sensibilization.

Key role for constitutive cyclooxygenase-2 of MDCK cells in basal signaling and response to released ATP

2001 ◽  
Vol 281 (2) ◽  
pp. C524-C531 ◽  
Author(s):  
Rennolds S. Ostrom ◽  
Caroline Gregorian ◽  
Ryan M. Drenan ◽  
Kathryn Gabot ◽  
Brinda K. Rana ◽  
...  
Keyword(s):  
Cell Function ◽  
Mdck Cells ◽  
Second Messengers ◽  
Atp Release ◽  
Cox Inhibitors ◽  
Cox 2 ◽  
Factor Α ◽  
Biochemical Activation ◽  
Camp Formation ◽  
Cox 1

Madin-Darby canine kidney (MDCK) cells release ATP upon mechanical or biochemical activation, initiating P2Y receptor signaling that regulates basal levels of multiple second messengers, including cAMP ( J Biol Chem 275: 11735–11739, 2000). Data shown here document inhibition of cAMP formation by Gd3+ and niflumic acid, channel inhibitors that block ATP release. cAMP production is stimulated via Ca2+-dependent activation of cytosolic phospholipase A2, release of arachidonic acid (AA), and cyclooxygenase (COX)-dependent production of prostaglandins, which activate prostanoid receptors coupled to Gs and adenylyl cyclase. In the current investigation, we assessed the expression and functional role of the two known isoforms of COX, COX-1 and COX-2. Treatment of cells with either a COX-1-selective inhibitor, SC-560, or COX-2-selective inhibitors, SC-58125 or NS-398, inhibited basal and UTP-stimulated cAMP levels. COX inhibitors also decreased forskolin-stimulated cAMP formation, implying this response is in part attributable to an action of AA metabolites. These findings imply an important role for the inducible form of COX, COX-2, under basal conditions. Indeed, COX-2 expression was readily detectable by immunoblot, and treatments that induce or reduce COX-2 expression in other cells (interleukin-1β, tumor necrosis factor-α, phorbol ester, or dexamethasone) had minimal or no effect on the levels of COX-2 immunoreactivity. RT-PCR using isoform-specific primers detected COX-2 mRNA. We conclude that COX-2 is constitutively expressed in MDCK-D1 cells and participates in basal and P2Y2-mediated signaling, implying a key role for COX-2 in regulation of epithelial cell function.

scholarly journals Ellagic acid inhibits lipopolysaccharide-induced expression of enzymes involved in the synthesis of prostaglandin E2 in human monocytes

2009 ◽  
Vol 103 (8) ◽  
pp. 1102-1109 ◽  
Author(s):  
Sofia Karlsson ◽  
Eewa Nånberg ◽  
Christina Fjaeraa ◽  
Jonny Wijkander
Keyword(s):  
Ellagic Acid ◽  
Inhibitory Effect ◽  
Ionophore A23187 ◽  
Human Monocytes ◽  
Cytosolic Phospholipase ◽  
Natural Polyphenol ◽  
The Subject ◽  
Cox 2 ◽  
Cancer And Inflammation ◽  
Cox 1

Ellagic acid, a natural polyphenol found in certain fruits, nuts and vegetables, has in recent years been the subject of intense research within the fields of cancer and inflammation. Pain, fever and swelling, all typical symptoms of inflammation, are ascribed to elevated levels of PGE2. In the present study, we have investigated the effects of ellagic acid on PGE2 release and on prostaglandin-synthesising enzymes in human monocytes. Ellagic acid was found to inhibit Ca ionophore A23187-, phorbol myristate acetate- and opsonised zymosan-induced release of PGE2 from monocytes pre-treated with the inflammatory agent lipopolysaccharide. Ellagic acid suppressed the lipopolysaccharide-induced increase in protein expression of cyclo-oxygenase-2 (COX-2), microsomal PGE synthase-1 (mPGEs-1) and cytosolic phospholipase A2α (cPLA2α), while it had no effect on the constitutively expressed COX-1 protein. Ellagic acid had no apparent inhibitory effect on these enzymes when the activities were determined in cell-free assays. We conclude that the inhibitory effect of ellagic acid on PGE2 release from monocytes is due to a suppressed expression of COX-2, mPGEs-1 and cPLA2α, rather than a direct effect on the activities of these enzymes.

scholarly journals New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5H)ones as Possible Anti-Inflammatory Agents

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 659
Author(s):  
Christophe Tratrat ◽  
Michelyne Haroun ◽  
Aliki Paparisva ◽  
Charalmpos Kamoutsis ◽  
Anthi Petrou ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Cyclooxygenase Inhibitors ◽  
Good Prediction ◽  
Docking Analysis ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Almost All ◽  
Inflammatory Action ◽  
Cox 1

Background: Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects. Methods: Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenan paw edema test. COX and LOX inhibitory actions were tested using ovine COX-1, human recombinant COX-2 and soybean LOX-1, respectively. Docking analysis was performed using Autodock. Results: All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis. Conclusions: A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms.

scholarly journals Characteristics of New Peptides GQLGEHGGAGMG, GEHGGAGMGGGQFQPV, EQGFLPGPEESGR, RLARAGLAQ, YGNPVGGVGH, and GNPVGGVGHGTTGT as Inhibitors of Enzymes Involved in Metabolic Syndrome and Antimicrobial Potential

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2492 ◽  
Author(s):  
Urszula Złotek ◽  
Anna Jakubczyk ◽  
Kamila Rybczyńska-Tkaczyk ◽  
Paula Ćwiek ◽  
Barbara Baraniak ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Antimicrobial Activity ◽  
Inhibitory Activity ◽  
Synthetic Peptides ◽  
Cytotoxic Effect ◽  
Inhibitory Effect ◽  
Converting Enzyme ◽  
Cox 2 ◽  
Enzyme I ◽  
Cox 1

The aim of this study was to determine the cytotoxic properties, influence on enzyme activity involved in metabolic syndrome, and antimicrobial activity of synthetic peptides with GQLGEHGGAGMG, GEHGGAGMGGGQFQPV, EQGFLPGPEESGR, RLARAGLAQ, YGNPVGGVGH, and GNPVGGVGHGTTGT sequences. Peptides have no cytotoxic effect on cells. The highest inhibitory effect on angiotensin converting enzyme I was noted for peptide GT-14 (IC50 = 525.63 µg/mL). None of the tested peptides had an influence on α-glucosidase. The highest α-amylase and lipase inhibitory activity was noted for GG-12 (IC50 = 56.72 and 60.62 µg/mL, respectively). The highest lipoxidase inhibitory activity was determined for peptide ER-13 (IC50 = 84.35 µg/mL). Peptide RQ-9 was characterized by the highest COX inhibitory activity (0.31 and 4.77 µg/mL for COX-1 and COX-2, respectively). Only peptide RQ-9 inhibited S. enteritidis ATCC 4931 growth (42–48%) in all tested concentrations (15.62–250 mg/mL).

scholarly journals In vitro Anti-inflammatory Activity of Ligustrum vulgare Extracts and Their Analytical Characterization

2013 ◽  
Vol 8 (11) ◽  
pp. 1934578X1300801 ◽  
Author(s):  
Anna Macková ◽  
Pavel Mučaji ◽  
Ute Widowitz ◽  
Rudolf Bauer
Keyword(s):  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Neutrophil Granulocytes ◽  
Cyclooxygenase 1 ◽  
Ligustrum Vulgare ◽  
China And Japan ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Interest in the anti-inflammatory effects of Ligustrum vulgare L., which has been used traditionally in China and Japan prompted us to determine anti-inflammatory effects of the plant's compounds in leukocytes. The leaves of L. vulgare were used to prepare a decoction which was successively extracted with organic solvents (dichloromethane (DCM), n-butanol, ethyl acetate) using liquid-liquid partition. Extracts were tested for inhibition of LTB4, resp. PGE2 biosynthesis. Each extract was evaluated for its in vitro cyclooxygenase-1/2 (COX-1/2) inhibitory activity using assays with purified COX-1 and COX-2 enzymes, as well as for their LTB4 formation inhibitory activity using an assay with activated human neutrophil granulocytes. All extracts reported inhibitory actions against COXs in comparison with the synthetic inhibitors NS-398 (IC50 = 2.6 μM) and indomethacin (IC50 = 0.9 μM). The dichloromethane extract of privet leaves showed a considerable inhibitory effect against COX-1 and COX-2 enzyme activity. The DCM extract revealed 2.7 times higher inhibitory activity against LTB4 formation in comparison with the known specific LT inhibitor zileuton (IC50 = 5.0 μM). Additionally, oleuropein and echinacoside were detected by HPLC-DAD and LC-MS in the Ligustrum vulgare leaves. Both compounds exhibited weak inhibitory activity on cyclooxygenases and leukotriene formation.

Isolation of (S)-(+)-Naproxene from Musa acuminata. Inhibitory Effect of Naproxene and its 7-Methoxy Isomer on Constitutive COX-1 and Inducible COX-2

Planta Medica ◽  
2000 ◽  
Vol 66 (5) ◽  
pp. 471-473 ◽  
Author(s):  
T. Abad ◽  
G. McNaughton-Smith ◽  
W. Q. Fletcher ◽  
F. Echeverri ◽  
R. Diaz-Peñate ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Musa Acuminata ◽  
Cox 2 ◽  
Cox 1

scholarly journals Compensatory Prostaglandin E2 Biosynthesis in Cyclooxygenase 1 or 2 Null Cells

1998 ◽  
Vol 187 (4) ◽  
pp. 517-523 ◽  
Author(s):  
Kanyawim Kirtikara ◽  
Scott G. Morham ◽  
Rajendra Raghow ◽  
Stanley J. F. Laulederkind ◽  
Takuro Kanekura ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Wild Type ◽  
Acidic Fibroblast Growth Factor ◽  
Cox Inhibitors ◽  
Cyclooxygenase 1 ◽  
Enhanced Expression ◽  
Key Enzyme ◽  
Cox 2 ◽  
Factor Α ◽  
Cox 1

Prostaglandin E2 (PGE2) production in immortalized, nontransformed cells derived from wild-type, cyclooxygenase 1–deficient (COX-1−/−) or cyclooxygenase 2–deficient (COX-2−/−) mice was examined after treatment with interleukin (IL)-1β, tumor necrosis factor α, acidic fibroblast growth factor, and phorbol ester (phorbol myristate acetate). Compared with their wild-type counterparts, COX-1−/− or COX-2−/− cells exhibited substantially enhanced expression of the remaining functional COX gene. Furthermore, both basal and IL-1–induced expression of cytosolic phospholipase A2 (cPLA2), a key enzyme-regulating substrate mobilization for PGE2 biosynthesis, was also more pronounced in both COX-1−/− and COX-2−/− cells. Thus, COX-1−/− and COX-2−/− cells have the ability to coordinate the upregulation of the alternate COX isozyme as well as cPLA2 genes to overcome defects in prostaglandin biosynthetic machinery. The potential for cells to alter and thereby compensate for defects in the expression of specific genes such as COX has significant clinical implications given the central role of COX in a variety of disease processes and the widespread use of COX inhibitors as therapeutic agents.

scholarly journals Modulation of Enzyme-Catalyzed Synthesis of Prostaglandins by Components Contained in Kidney Microsomal Preparations

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 219
Author(s):  
Hyoung-Woo Bai ◽  
Jina Yu ◽  
Yue Wang ◽  
Pan Wang ◽  
Baoting Zhu
Keyword(s):  
Acid Metabolism ◽  
Inhibitory Effect ◽  
Arachidonic Acid Metabolism ◽  
Microsomal Preparation ◽  
Pig Kidney ◽  
Cyclooxygenase 1 ◽  
Kidney Microsomes ◽  
Cox 2 ◽  
Cox 1

In the kidney, prostaglandins formed by cyclooxygenase 1 and 2 (COX-1 and COX-2) play an important role in regulating renal blood flow. In the present study, we report our observations regarding a unique modulatory effect of renal microsomal preparation on COX-1/2-mediated formation of major prostaglandin (PG) products in vitro. We found that microsomes prepared from pig and rat kidneys had a dual stimulatory–inhibitory effect on the formation of certain PG products catalyzed by COX-1 and COX-2. At lower concentrations, kidney microsomes stimulated the formation of certain PG products, whereas at higher concentrations, their presence inhibited the formation. Presence of kidney microsomes consistently increased the Km values of the COX-1/2-mediated reactions, while the Vmax might be increased or decreased depending on stimulation or inhibition observed. Experimental evidence was presented to show that a protein component present in the pig kidney microsomes was primarily responsible for the activation of the enzyme-catalyzed arachidonic acid metabolism leading to the formation of certain PG products.

scholarly journals A new 14,15-dinor-labdane Glucoside from Crassocephalum Mannii

2008 ◽  
Vol 3 (6) ◽  
pp. 1934578X0800300
Author(s):  
Mohamed-Elamir F. Hegazy ◽  
Ashraf A. Aly ◽  
Ahmed A. Ahmed ◽  
Djemgou C. Pierre ◽  
Pierre Tane ◽  
...  
Keyword(s):  
Spectroscopic Analysis ◽  
Inhibitory Effect ◽  
H Nmr ◽  
Aerial Parts ◽  
Cox 2 ◽  
Cox 1 ◽  
C Nmr

A new 14,15-dinor-labdane glucoside, named crassoside A (1), was isolated from the aerial parts of Crassocephalum mannii. The structure of 1 was elucidated on the basis of spectroscopic analysis (1H NMR, 13C NMR, HMQC, HMBC and NOEs). Compound 1 demonstrated a low inhibitory effect against COX-1, but was inactive against COX-2.

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