Effects of chlorinated biphenyls and metabolites on human uterine myocyte proliferation

2007 ◽  
Vol 26 (10) ◽  
pp. 801-809 ◽  
Author(s):  
Carolina Bredhult ◽  
Britt-Marie Bäcklin ◽  
Matts Olovsson
Keyword(s):  
Menstrual Cycle ◽  
Pregnant Women ◽  
Proliferative Activity ◽  
Myometrial Cell ◽  
Myometrial Cells ◽  
Endocrine Disrupting ◽  
17Β Estradiol ◽  
Brdu Assay ◽  
Myocyte Proliferation

Uterine myometrial cells are responsive to sex steroids, which could make them susceptible to actions of endocrine disrupting environmental contaminants such as some PCBs. The aim of this investigation was to identify possible effects of some chlorinated biphenyls (CBs) and their metabolites on myometrial cell proliferation. Myometrial cells obtained from women in both phases of the menstrual cycle and from pregnant women were grown in vitro and exposed to CB 101, CB 118, 3' -MeSO2CB 101, 4'-MeSO2-CB 101, 4-OH-CB 107, 17 β-estradiol, progesterone, ethinylestradiol or levonorgestrel. The proliferative activity was studied by a BrdU assay. Myometrial cell cultures originating from pregnant women exhibited decreased proliferation in response to 3'-MeSO 2-CB 101, 4'-MeSO2-CB 101 and 4-OH-CB 107. Estradiol, a combination of 1 nM 17β-estradiol and 10 nM progesterone, ethinylestradiol and levonorgestrel also reduced the proliferation of the myometrial cells, regardless of whether the cells were collected from either of the menstrual cycle phases or from pregnant women. To our knowledge this study is the first to demonstrate that some CBs affect the proliferative activity of human uterine myocytes. Human & Experimental Toxicology (2007) 26, 801— 809

scholarly journals Presence, Actions, and Regulation of Myostatin in Rat Uterus and Myometrial Cells

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 906-914 ◽  
Author(s):  
Pasquapina Ciarmela ◽  
Ezra Wiater ◽  
Sean M. Smith ◽  
Wylie Vale
Keyword(s):  
Cell Line ◽  
Estrous Cycle ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Rat Uterus ◽  
Myometrial Cell ◽  
Myometrial Cells ◽  
Myocyte Proliferation

Myostatin, a member of the TGF-β superfamily of proteins, is known to suppress skeletal muscle mass and myocyte proliferation. The muscular component of the uterus is the myometrium, a tissue that regulates its mass in response to different physiological conditions under the influence of sex steroids. Recently, our laboratory reported effects of activin-A, another TGF-β family member, on signalling and proliferation of rat uterine explants and human myometrial cell lines in culture. Here, we explore the expression, actions, and regulation of myostatin in uterine smooth muscle. Myostatin mRNA was demonstrated to be expressed in a myometrial cell line, pregnant human myometrial 1 cell line (PHM1). Functional assays showed that myostatin induced phosphorylation of Smad-2 and reduced proliferation of PHM1 number in a time and dose-dependent manner. Furthermore, myostatin activated smad-2 specific signalling pathways in rat uterine explants. To expand on our in vitro findings, we found that myostatin is expressed in rat uterus and determined that myostatin mRNA expression varies as a function of the phase of the estrous cycle. Uterine levels of myostatin peaked during late estrus and were the lowest at proestrus. Ovariectomy increased myostatin expression; estrogen treatment strongly decreased myostatin levels, whereas progesterone weakly decreased myostatin expression. In conclusion, myometrial cells are myostatin sensitive, myostatin mRNA levels are modulated in vivo in rats during the estrous cycle, and in response to steroid deprivation and replacement. Myometrial cells are myostatin-sensitive; myostatin mRNA levels are modulated in rats during the estrous cycle and in response to steroid deprivation and replacement.

scholarly journals Investigation of In Vitro Endocrine Activities of Microcystis and Planktothrix Cyanobacterial Strains

Toxins ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 228 ◽  
Author(s):  
Vittoria Mallia ◽  
Lada Ivanova ◽  
Gunnar S. Eriksen ◽  
Emma Harper ◽  
Lisa Connolly ◽  
...  
Keyword(s):  
Relative Concentration ◽  
Liver Microsomes ◽  
Endocrine Disrupting Compounds ◽  
Bioactive Metabolites ◽  
Global Challenge ◽  
Endocrine Disrupting ◽  
Agonist And Antagonist ◽  
17Β Estradiol ◽  
Potential Risks

Cyanobacteria are cosmopolitan photosynthetic prokaryotes that can form dense accumulations in aquatic environments. They are able to produce many bioactive metabolites, some of which are potentially endocrine disrupting compounds, i.e., compounds that interfere with the hormonal systems of animals and humans. Endocrine disruptors represent potential risks to both environmental and human health, making them a global challenge. The aim of this study was to investigate the potential endocrine disrupting activities with emphasis on estrogenic effects of extracts from cultures of Microcystis or Planktothrix species. We also assessed the possible role of microcystins, some of the most studied cyanobacterial toxins, and thus included both microcystin-producing and non-producing strains. Extracts from 26 cyanobacterial cultures were initially screened in estrogen-, androgen-, and glucocorticoid-responsive reporter-gene assays (RGAs) in order to identify endocrine disruption at the level of nuclear receptor transcriptional activity. Extracts from selected strains were tested repeatedly in the estrogen-responsive RGAs, but the observed estrogen agonist and antagonist activity was minor and similar to that of the cyanobacteria growth medium control. We thus focused on another, non-receptor mediated mechanism of action, and studied the 17β-estradiol (natural estrogen hormone) biotransformation in human liver microsomes in the presence or absence of microcystin-LR (MC-LR), or an extract from the MC-LR producing M. aeruginosa PCC7806 strain. Our results show a modulating effect on the estradiol biotransformation. Thus, while 2-hydroxylation was significantly decreased following co-incubation of 17β-estradiol with MC-LR or M. aeruginosa PCC7806 extract, the relative concentration of estrone was increased.

scholarly journals Estrogenic activity in reused water: comparison of concentration methods

2021 ◽  
Vol 5 (3) ◽  
pp. 125-130
Author(s):  
Natasha Berendonk Handam
Keyword(s):  
Solid Phase Extraction ◽  
Estrogenic Activity ◽  
Solid Phase ◽  
Total Concentration ◽  
Alternative Methods ◽  
Phase Extraction ◽  
Endocrine Disrupting ◽  
17Β Estradiol ◽  
Concentration Methods

Determining the presence of endocrine disrupting substances in waters is a relevant aspect for monitoring environmental health. Given its relevance, it is important to use methods that can make the total concentration of substances with estrogenic activity (eg endocrine disruptors), being faster, and without the use of compounds that pollute the environment. The purpose of the study was to compare the effectiveness of the methods of concentration by lyophilization and by vacuum concentration of substances with estrogenic activity present in reused water, using the commonly used methodology, solid phase extraction. Three methods were compared: solid phase extraction, lyophilization, and vacuum centrifugation. Sample aliquots of reused water received 17β-estradiol at a final concentration of 2 μg L-1 and were concentrated by the three methods. The analysis of estrogenic activity was performed by the in vitro YES (Yeast Estrogen Screen) assay. The results showed that the vacuum centrifugation, solid phase extraction and lyophilization methods had different percentages in the recovery of substances with estrogenic activity, being 45%, 40%, and 31%, respectively. The study pointed out that the lyophilization and vacuum centrifugation methods were effective as alternative methods for concentrating samples containing substances with estrogenic activity.

A critical role for PKCζ in endothelin-1-induced uterine contractions at the end of pregnancy

2003 ◽  
Vol 285 (3) ◽  
pp. C599-C607 ◽  
Author(s):  
G. Di Liberto ◽  
E. Dallot ◽  
I. Eude-Le Parco ◽  
D. Cabrol ◽  
F. Ferré ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Contractile Response ◽  
Critical Role ◽  
Significant Loss ◽  
Inhibitory Peptide ◽  
Lattice Contraction ◽  
Myometrial Cell ◽  
Endothelin 1 ◽  
Myometrial Cells

We have previously shown that protein kinase C (PKC) ζ and/or PKCδ are necessary for endothelin-1 (ET-1)-induced human myometrial contraction at the end of pregnancy (Eude I, Paris P, Cabrol D, Ferré F, and Breuiller-Fouché M. Biol Reprod 63: 1567–1573, 2000). Here, we report that the selective inhibitor of PKCδ isoform, Rottlerin, does not prevent ET-1-induced contractions, whereas LY-294002, a phosphatidylinositol (PI) 3-kinase inhibitor, affects the contractile response. This study characterized the in vitro contractile response of cultured human pregnant myometrial cells to ET-1 known to induce in vitro contractions of intact uterine smooth muscle strips. Cultured myometrial cells incorporated into collagen lattices have the capacity to reduce the size of these lattices, referred to as lattice contraction. Neither the selective conventional PKC isoform inhibitor, Gö-6976, or rottlerin affected myometrial cell-mediated gel contraction by ET-1, whereas this effect was blocked by LY-294002. We found that treatment of myometrial cell lattices with an inhibitory peptide specific for PKCζ or with an antisense against PKCζ resulted in a significant loss of ET-1-induced contraction. Evidence is also presented by using confocal microscopy that ET-1 induced translocation of PKCζ to a structure coincident with the actin-rich microfilaments of the cytoskeleton. We have shown that PKCζ has a role in the actin organization in ET-1-stimulated cells. Accordingly, our results suggest that PKCζ plays a role in myometrial contraction in pregnant women.

Balancing the budget of environmental estrogen exposure: the contribution of recycled water

2009 ◽  
Vol 60 (4) ◽  
pp. 1003-1012 ◽  
Author(s):  
Frederic D. L. Leusch ◽  
Michael R. Moore ◽  
Heather F. Chapman
Keyword(s):  
Endocrine Disrupting Compounds ◽  
Dietary Intakes ◽  
Recycled Water ◽  
Environmental Media ◽  
Estrogen Exposure ◽  
Treated Sewage ◽  
Endocrine Disrupting ◽  
17Β Estradiol

Estrogenic endocrine disrupting compounds (e-EDCs) are present in treated sewage and there is concern about estrogenicity of potable recycled water. However e-EDCs are also present in other environmental media and intake from water needs to be considered in relation to these other sources. The concentrations of 13 e-EDCs in foodstuffs and drinking water are reviewed, their predicted concentrations in recycled water are estimated, and the daily estrogenic intake as 17β-estradiol equivalent (EEq) based on both in vitro and in vivo potencies is calculated as 1.39 and 9.65 μg EEq/d, respectively. Dietary intake accounts for more than 99.8% of that total, and more than 84.2% is due to phytosterols. Drinking 2 L of recycled water per day is expected to add 0.001 to 0.016 μg EEq/d based on in vitro and in vivo potencies, respectively. Exposure to e-EDCs in recycled water is therefore likely to be insignificant compared to current dietary intakes.

(Substituted)-benzo[b]thiophene-4-carboxamide Synthesis and Antiproliferative Activity Study

2020 ◽  
Vol 17 (5) ◽  
pp. 563-573 ◽  
Author(s):  
Chandrakant Dhondiram Pawar ◽  
Dattatraya Navnath Pansare ◽  
Devanand Baburao Shinde
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Proliferative Activity ◽  
Thiophene Ring ◽  
Amide Group ◽  
Peptide Coupling ◽  
Ic50 Value ◽  
Important Building Block ◽  
Mcf 7

Background: Thiophene ring forms important building block in medicinal chemistry. Literature reveals that thiophene ring in combination with different groups shows different activity. By keeping these things in mind we have designed and synthesized a new series of amide and sulfonamide coupled thiophene. A series of novel substituted 3-sulfamoylbenzo[b]thiophene-4- carboxamide molecules containing sulfonamide and amide group were designed, synthesized and used for anti-proliferative activity study. Methods: The final compounds 16-36 were synthesized by using series of reactions comprising sulfonation, sulfonamide coupling, hydrolysis and peptide coupling. The yields of compounds 16- 36 are in the range of 90-98%. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR, LCMS and the purity was checked through HPLC analysis. The compounds were further tested for their in vitro anticancer activity against a series of cell lines A549, HeLa, MCF-7 and Du-145. Results: The intermediates 8-13, 15 and final compounds 16-36 were synthesized in good yields. The synthesized compounds were further tested for their anticancer activity and most of compounds showed moderate to good anticancer activity against all four cell lines. Conclusion: We have synthesized 21 compounds and were screened for anticancer activity against MCF-7, HeLa, A-549 and Du-145 cancer cell lines. Most of the compounds were active for tested cell lines with IC50 value in the range of 1.81 to 9.73 μM. The compounds 18, 19, 21, 25, 30, 31 and 33 are most active in cell line data with IC50 value in the range of 1.81 to 2.52 μM.

Discovery of N-Phenyl-4-(1H-pyrrol-3-yl)pyrimidin-2-amine Derivatives as Potent Mnk2 Inhibitors: Design, Synthesis, SAR Analysis, and Evaluation of in vitro Anti-leukaemic Activity

2019 ◽  
Vol 15 (6) ◽  
pp. 602-623 ◽  
Author(s):  
Ahmed M. Abdelaziz ◽  
Sarah Diab ◽  
Saiful Islam ◽  
Sunita K.C. Basnet ◽  
Benjamin Noll ◽  
...  
Keyword(s):  
Proliferative Activity ◽  
Myeloid Cell ◽  
Structural Diversity ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Cell Leukaemia ◽  
Aberrant Expression ◽  
Design Synthesis ◽  
Induced Apoptosis

Background:Aberrant expression of eukaryotic translation initiation factor 4E (eIF4E) is common in many types of cancer including acute myeloid leukaemia (AML). Phosphorylation of eIF4E by MAPK-interacting kinases (Mnks) is essential for the eIF4E-mediated oncogenic activity. As such, the pharmacological inhibition of Mnks can be an effective strategy for the treatment of cancer.Methods:A series of N-phenyl-4-(1H-pyrrol-3-yl)pyrimidin-2-amine derivatives was designed and synthesised. The Mnk inhibitory activity of these derivatives as well as their anti-proliferative activity against MV4-11 AML cells was determined.Results:These compounds were identified as potent Mnk2 inhibitors. Most of them demonstrated potent anti-proliferative activity against MV4-11 AML cells. The cellular mechanistic studies of the representative inhibitors revealed that they reduced the level of phosphorylated eIF4E and induced apoptosis by down-regulating the anti-apoptotic protein myeloid cell leukaemia 1 (Mcl-1) and by cleaving poly(ADP-ribose)polymerase (PARP). The lead compound 7k possessed desirable pharmacokinetic properties and oral bioavailability.Conclusion:This work proposes that exploration of the structural diversity in the context of Nphenyl- 4-(1H-pyrrol-3-yl)pyrimidin-2-amine would offer potent and selective Mnk inhibitors.

scholarly journals Electrochemotherapy with Calcium Chloride and 17β-Estradiol Modulated Viability and Apoptosis Pathway in Human Ovarian Cancer

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 19
Author(s):  
Zofia Łapińska ◽  
Michał Dębiński ◽  
Anna Szewczyk ◽  
Anna Choromańska ◽  
Julita Kulbacka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Calcium Chloride ◽  
Morphological Changes ◽  
Cell Membrane Permeability ◽  
Immunocytochemical Staining ◽  
Ovarian Cancer Cells ◽  
Apoptosis Pathway ◽  
17Β Estradiol

Estrogens (Es) play a significant role in the carcinogenesis and progression of ovarian malignancies. Depending on the concentration, Es may have a protective or toxic effect on cells. Moreover, they can directly or indirectly affect the activity of membrane ion channels. In the presented study, we investigated in vitro the effectiveness of the ovarian cancer cells (MDAH-2774) pre-incubation with 17β-estradiol (E2; 10 µM) in the conventional chemotherapy (CT) and electrochemotherapy (ECT) with cisplatin or calcium chloride. We used three different protocols of electroporation including microseconds (µsEP) and nanoseconds (nsEP) range. The cytotoxic effect of the applied treatment was examined by the MTT assay. We used fluorescent staining and holotomographic imaging to observe morphological changes. The immunocytochemical staining evaluated the expression of the caspase-12. The electroporation process’s effectiveness was analyzed by a flow cytometer using the Yo-Pro™-1 dye absorption assay. We found that pre-incubation of ovarian cancer cells with 17β-estradiol may effectively enhance the chemo- and electrochemotherapy with cisplatin and calcium chloride. At the same time, estradiol reduced the effectiveness of electroporation, which may indicate that the mechanism of increasing the effectiveness of ECT by E2 is not related to the change of cell membrane permeability.

scholarly journals Cell-derived Extracellular Matrix as maintaining Biomaterial for adipogenic differentiation

2020 ◽  
Vol 6 (3) ◽  
pp. 410-413
Author(s):  
Petra J. Kluger ◽  
Svenja Nellinger ◽  
Simon Heine ◽  
Ann-Cathrin Volz
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Adipogenic Differentiation ◽  
Cellular Activity ◽  
Adipose Tissue Engineering ◽  
Physical Support ◽  
Supporting Effect ◽  
Brdu Assay ◽  
The Impact

AbstractThe extracellular matrix (ECM) naturally surrounds cells in humans, and therefore represents the ideal biomaterial for tissue engineering. ECM from different tissues exhibit different composition and physical characteristics. Thus, ECM provides not only physical support but also contains crucial biochemical signals that influence cell adhesion, morphology, proliferation and differentiation. Next to native ECM from mature tissue, ECM can also be obtained from the in vitro culture of cells. In this study, we aimed to highlight the supporting effect of cell-derived- ECM (cdECM) on adipogenic differentiation. ASCs were seeded on top of cdECM from ASCs (scdECM) or pre-adipocytes (acdECM). The impact of ECM on cellular activity was determined by LDH assay, WST I assay and BrdU assay. A supporting effect of cdECM substrates on adipogenic differentiation was determined by oil red O staining and subsequent quantification. Results revealed no effect of cdECM substrates on cellular activity. Regarding adipogenic differentiation a supporting effect of cdECM substrates was obtained compared to control. With these results, we confirm cdECM as a promising biomaterial for adipose tissue engineering.

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