Anthonotha macrophylla P. Beauv (Caesalpiniaceae) aqueous extract exhibits antiestrogenic effects in vitro and in vivo

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Telesphore Nanbo Gueyo ◽  
Marie Alfrede Mvondo ◽  
Stéphane Zingue ◽  
Marius Trésor Kemegne Sipping ◽  
Larissa Vanelle Kenmogne ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Aqueous Extract ◽  
Mass Spectrometry Analysis ◽  
Spectrometry Analysis ◽  
Flight Mass Spectrometry ◽  
Estrogen Receptor Modulators ◽  
Mcf 7 ◽  
Antiestrogenic Effects

AbstractBackgroundPhytoestrogens are natural compounds known as natural selective estrogen receptor modulators used as alternatives against estrogen-dependent cancers. This study aims to evaluate the antiestrogenic effects of Anthonotha macrophylla, a plant used to treat cancer in Cameroon.MethodsThe estrogenic/antiestrogenic activities of A. macrophylla aqueous extract were evaluated in vitro using MCF-7 cell proliferation assay. Moreover, a classical uterotrophic test was carried out to evaluate the antiestrogenic effects of A. macrophylla in rats. Changes in the uterus, vagina, and mammary glands were used as endpoints of estrogenicity.ResultsAnthonotha macrophylla induced antiestrogenic effects in vitro at all the tested concentrations by inhibiting estradiol-induced MCF-7 cell proliferation (p < 0.001). In vivo, a coadministration of estradiol with A. macrophylla extract led to the decrease of uterine [150 (p < 0.05) and 300 (p < 0.01) mg/kg body weight (BW)] and vaginal [75 (p < 0.01) and 300 (p < 0.05) mg/kg BW] epithelial thickness. In addition, a reduction in the mammary gland acini lumen’s diameter was also observed at 75 and 150 mg/kg. Gas chromatography-time-of-flight-mass spectrometry analysis showed that phenolic acid derivatives are present in A. macrophylla extract, which are well known to be endowed with estrogenic/antiestrogenic properties. The LD50 of A. macrophylla was estimated to be less than 2000 mg/kg.ConclusionsAnthonotha macrophylla aqueous extract has antiestrogenic properties. This could promote more studies to explore its ability to prevent estrogen-dependent cancers.

scholarly journals Inhibition of MCF-7 breast cancer cell proliferation by 5alpha-dihydrotestosterone; a role for p21(Cip1/Waf1)

2004 ◽  
Vol 32 (3) ◽  
pp. 793-810 ◽  
Author(s):  
MA Greeve ◽  
RK Allan ◽  
JM Harvey ◽  
JM Bentel
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
S Phase ◽  
Cyclin D3 ◽  
P27 Kip1 ◽  
Mcf 7

Androgens inhibit the growth of breast cancer cells in vitro and in vivo by mechanisms that remain poorly defined. In this study, treatment of asynchronously growing MCF-7 breast cancer cells with the androgen, 5alpha-dihydrotestosterone (DHT), was shown to inhibit cell proliferation and induce moderate increases in the proportion of G1 phase cells. Consistent with targeting the G1-S phase transition, DHT pretreatment of MCF-7 cultures impeded the serum-induced progression of G1-arrested cells into S phase and reduced the kinase activities of cyclin-dependent kinase (Cdk)4 and Cdk2 to less than 50% of controls within 3 days. DHT treatment was associated with greater than twofold increases in the levels of the Cdk inhibitor, p27(Kip1), while p21(Cip1/Waf1) protein levels remained unchanged. During the first 24 h of DHT treatment, levels of Cdk4-associated p21(Cip1/Waf1) and p27(Kip1) were reduced coinciding with decreased levels of Cdk4-associated cyclin D3. In contrast, DHT treatment caused increased accumulation of Cdk2-associated p21(Cip1/Waf1), with no significant alterations in levels of p27(Kip1) bound to Cdk2 complexes. These findings suggest that DHT reverses the Cdk4-mediated titration of p21(Cip1/Waf1) and p27(Kip1) away from Cdk2 complexes, and that the increased association of p21(Cip1/Waf1) with Cdk2 complexes in part mediates the androgen-induced growth inhibition of breast cancer cells.

scholarly journals Phytotoxicity of Essential Oils on Selected Weeds: Potential Hazard on Food Crops

Plants ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 79 ◽  
Author(s):  
María Ibáñez ◽  
María Blázquez
Keyword(s):  
Seed Germination ◽  
Essential Oil ◽  
Essential Oils ◽  
Mass Spectrometry Analysis ◽  
Gas Chromatography Mass Spectrometry ◽  
Food Crops ◽  
Potential Hazard ◽  
Spectrometry Analysis

The chemical composition of winter savory, peppermint, and anise essential oils, and in vitro and in vivo phytotoxic activity against weeds (Portulaca oleracea, Lolium multiflorum, and Echinochloa crus-galli) and food crops (maize, rice, and tomato), have been studied. Sixty-four compounds accounting for between 97.67–99.66% of the total essential oils were identified by Gas Chromatography-Mass Spectrometry analysis. Winter savory with carvacrol (43.34%) and thymol (23.20%) as the main compounds produced a total inhibitory effect against the seed germination of tested weed. Menthol (48.23%), menthone (23.33%), and iso-menthone (16.33%) from peppermint only showed total seed germination inhibition on L. multiflorum, whereas no significant effects were observed with trans-anethole (99.46%) from anise at all concentrations (0.125–1 µL/mL). Low doses of peppermint essential oil could be used as a sustainable alternative to synthetic agrochemicals to control L. multiflorum. The results corroborate that in vivo assays with a commercial emulsifiable concentrate need higher doses of the essential oils to reproduce previous in vitro trials. The higher in vivo phytotoxicity of winter savory essential oil constitutes an eco-friendly and less pernicious alternative to weed control. It is possible to achieve a greater in vivo phytotoxicity if less active essential oil like peppermint is included with other active excipients.

Corona protein impacts on alternating current biosusceptometry signal and circulation times of differently coated MnFe2O4 nanoparticles

Nanomedicine ◽  
2021 ◽  
Author(s):  
Andre Gonçalves Prospero ◽  
Lais Pereira Buranello ◽  
Carlos AH Fernandes ◽  
Lucilene Delazari dos Santos ◽  
Guilherme Soares ◽  
...  
Keyword(s):  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Bovine Serum ◽  
Signal Intensity ◽  
Alternating Current ◽  
Circulation Time ◽  
Mass Spectrometry Analysis ◽  
Spectrometry Analysis

Background: We evaluated the impacts of corona protein (CP) formation on the alternating current biosusceptometry (ACB) signal intensity and in vivo circulation times of three differently coated magnetic nanoparticles (MNP): bare, citrate-coated and bovine serum albumin-coated MNPs. Methods: We employed the ACB system, gel electrophoresis and mass spectrometry analysis. Results: Higher CP formation led to a greater reduction in the in vitro ACB signal intensity and circulation time. We found fewer proteins forming the CP for the bovine serum albumin-coated MNPs, which presented the highest circulation time in vivo among the MNPs studied. Conclusion: These data showed better biocompatibility, stability and magnetic signal uniformity in biological media for bovine serum albumin-coated MNPs than for citrate-coated MNPs and bare MNPs.

scholarly journals Thiol Peroxidase Is an Important Component of Streptococcus pneumoniae in Oxygenated Environments

2012 ◽  
Vol 80 (12) ◽  
pp. 4333-4343 ◽  
Author(s):  
Barak Hajaj ◽  
Hasan Yesilkaya ◽  
Rachel Benisty ◽  
Maayan David ◽  
Peter W. Andrew ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mass Spectrometry Analysis ◽  
Activity Levels ◽  
Content Type ◽  
Spectrometry Analysis ◽  
Cellular Processes ◽  
Thiol Peroxidase ◽  
Fine Tune

ABSTRACTStreptococcus pneumoniaeis an aerotolerant Gram-positive bacterium that causes an array of diseases, including pneumonia, otitis media, and meningitis. During aerobic growth,S. pneumoniaeproduces high levels of H2O2. SinceS. pneumoniaelacks catalase, the question of how it controls H2O2levels is of critical importance. Thepsalocus encodes an ABC Mn2+-permease complex (psaBCA) and a putative thiol peroxidase,tpxD. This study shows thattpxDencodes a functional thiol peroxidase involved in the adjustment of H2O2homeostasis in the cell. Kinetic experiments showed that recombinant TpxD removed H2O2efficiently. However,in vivoexperiments revealed that TpxD detoxifies only a fraction of the H2O2generated by the pneumococcus. Mass spectrometry analysis demonstrated that TpxD Cys58undergoes selective oxidationin vivo, under conditions where H2O2is formed, confirming the thiol peroxidase activity. Levels of TpxD expression and synthesisin vitrowere significantly increased in cells grown under aerobic versus anaerobic conditions. The challenge with D39 and TIGR4 with H2O2resulted intpxDupregulation, whilepsaBCAexpression was oppositely affected. However, the challenge of ΔtpxDmutants with H2O2did not affectpsaBCA, implying that TpxD is involved in the regulation of thepsaoperon, in addition to its scavenging activity. Virulence studies demonstrated a notable difference in the survival time of mice infected intranasally with D39 compared to that of mice infected intranasally with D39ΔtpxD. However, when bacteria were administered directly into the blood, this difference disappeared. The findings of this study suggest that TpxD constitutes a component of the organism's fundamental strategy to fine-tune cellular processes in response to H2O2.

‘In vivo’ and ‘in vitro’ activity of Larrea divaricata Cav. on EL-4 cells

2010 ◽  
Vol 30 (8) ◽  
pp. 965-971 ◽  
Author(s):  
Roberto Davicino ◽  
Rosario Alonso ◽  
Claudia Anesini
Keyword(s):  
Cell Proliferation ◽  
Aqueous Extract ◽  
Tritiated Thymidine ◽  
Folk Medicine ◽  
Thymidine Uptake ◽  
Stimulatory Action ◽  
T Lymphoma ◽  
Larrea Divaricata

Larrea divaricata is a plant widely used in folk medicine in Argentina. It has been demonstrated that an aqueous extract of L. divaricata possesses a biphasic effect on cell proliferation, at low concentrations exerts a stimulatory action and at high concentrations exerts anti-proliferative effects upon the T lymphoma BW 5147; therefore, we propose in this paper to test the effect of the extract ‘in vitro’ and ‘in vivo’ in another T-cell lymphoma named EL-4. It was analyzed ‘in vitro’ cell proliferation by tritiated thymidine uptake and the effect of the extract on tumors induced in mice analyzing tumor progression and survival.The results showed that the aqueous extract induced the proliferation of tumor cells at all the concentrations studied. The results ‘in vivo’ showed that the aqueous extract stimulated significantly the size of tumors and that untreated mice lived longer than those treated. It is important to be very careful when plant extracts are selected for the treatment of several diseases. Consequently, before using a plant extract, specific scientific studies must be undertaken on different models to certificate therapeutic and adverse effects. Moreover, it can be said that L. divaricata has a specific anti-tumor mechanism of action depending on the targets.

scholarly journals Hemolymph Melanization in the Silkmoth Bombyx mori Involves Formation of a High Molecular Mass Complex That Metabolizes Tyrosine

2013 ◽  
Vol 288 (20) ◽  
pp. 14476-14487 ◽  
Author(s):  
Kevin D. Clark ◽  
Michael R. Strand
Keyword(s):  
Complex Formation ◽  
Bombyx Mori ◽  
Gel Filtration ◽  
High Molecular Mass ◽  
Mass Spectrometry Analysis ◽  
High Mass ◽  
Wound Site ◽  
Spectrometry Analysis

The phenoloxidase (PO) cascade regulates the melanization of blood (hemolymph) in insects and other arthropods. Most studies indicate that microbial elicitors activate the PO cascade, which results in processing of the zymogen PPO to PO. PO is then thought to oxidize tyrosine and o-diphenols to quinones, which leads to melanin. However, different lines of investigation raise questions as to whether these views are fully correct. Here we report that hemolymph from the silkmoth, Bombyx mori, rapidly melanizes after collection from a wound site. Prior studies indicated that in vitro activated PPO hydroxylates Tyr inefficiently. Measurement of in vivo substrate titers, however, suggested that Tyr was the only PO substrate initially present in B. mori plasma and that it is rapidly metabolized by PO. Fractionation of plasma by gel filtration chromatography followed by bioassays indicated that melanization activity was primarily associated with a high mass complex (∼670 kDa) that contained PO. The prophenoloxidase-activating protease inhibitor Egf1.0 blocked formation of this complex and Tyr metabolism, but the addition of phenylthiourea to plasma before fractionation enhanced complex formation and Tyr metabolism. Mass spectrometry analysis indicated that the complex contained PO plus other proteins. Taken together, our results indicate that wounding alone activates the PO cascade in B. mori. They also suggest that complex formation is required for efficient use of Tyr as a substrate.

scholarly journals circPDE4B prevents articular cartilage degeneration and promotes repair by acting as a scaffold for RIC8A and MID1

2021 ◽  
pp. annrheumdis-2021-219969
Author(s):  
Shuying Shen ◽  
Yute Yang ◽  
Panyang Shen ◽  
Jun Ma ◽  
Bin Fang ◽  
...  
Keyword(s):  
Rna Binding ◽  
Cartilage Degeneration ◽  
Mitogen Activated Protein Kinase ◽  
Mass Spectrometry Analysis ◽  
Circular Rnas ◽  
Nucleotide Exchange ◽  
Spectrometry Analysis

ObjectivesCircular RNAs (circRNAs) have emerged as significant biological regulators. Herein, we aimed to elucidate the role of an unidentified circRNA (circPDE4B) that is reportedly downregulated in osteoarthritis (OA) tissues.MethodsThe effects of circPDE4B were explored in human and mouse chondrocytes in vitro. Specifically, RNA pull-down (RPD)-mass spectrometry analysis (MS), immunoprecipitation, glutathione-S-transferase (GST) pull-down, RNA immunoprecipitation and RPD assays were performed to verify the interactions between circPDE4B and the RIC8 guanine nucleotide exchange factor A (RIC8A)/midline 1 (MID1) complex. A mouse model of OA was also employed to confirm the role of circPDE4B in OA pathogenesis in vivo.ResultscircPDE4B regulates chondrocyte cell viability and extracellular matrix metabolism. Mechanistically, FUS RNA binding protein (FUS) was found to promote the splicing of circPDE4B, while downregulation of circPDE4B in OA is partially caused by upstream inhibition of FUS. Moreover, circPDE4B facilitates the association between RIC8A and MID1 by acting as a scaffold to promote RIC8A degradation through proteasomal degradation. Furthermore, ubiquitination of RIC8A at K415 abrogates RIC8A degradation. The circPDE4B–RIC8A axis was observed to play an important role in regulating downstream p38 mitogen-activated protein kinase (MAPK) signalling. Furthermore, delivery of a circPDE4B adeno-associated virus (AAV) abrogates the breakdown of cartilage matrix by medial meniscus destabilisation in mice, whereas a RIC8A AAV induces the opposite effect.ConclusionThis work highlights the function of the circPDE4B–RIC8A axis in OA joints, as well as its regulation of MAPK-p38, suggesting this axis as a potential therapeutic target for OA.

scholarly journals Cell cycle–dependent association of polo kinase Cdc5 with CENP-A contributes to faithful chromosome segregation in budding yeast

2019 ◽  
Vol 30 (8) ◽  
pp. 1020-1036 ◽  
Author(s):  
Prashant K. Mishra ◽  
Gudjon Olafsson ◽  
Lars Boeckmann ◽  
Timothy J. Westlake ◽  
Ziad M. Jowhar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Mass Spectrometry Analysis ◽  
Spectrometry Analysis ◽  
Growth Defects ◽  
Evolutionarily Conserved ◽  
Histone H3 Variant ◽  
Cycle Dependent

Evolutionarily conserved polo-like kinase, Cdc5 (Plk1 in humans), associates with kinetochores during mitosis; however, the role of cell cycle–dependent centromeric ( CEN) association of Cdc5 and its substrates that exclusively localize to the kinetochore have not been characterized. Here we report that evolutionarily conserved CEN histone H3 variant, Cse4 (CENP-A in humans), is a substrate of Cdc5, and that the cell cycle–regulated association of Cse4 with Cdc5 is required for cell growth. Cdc5 contributes to Cse4 phosphorylation in vivo and interacts with Cse4 in mitotic cells. Mass spectrometry analysis of in vitro kinase assays showed that Cdc5 phosphorylates nine serine residues clustered within the N-terminus of Cse4. Strains with cse4-9SA exhibit increased errors in chromosome segregation, reduced levels of CEN-associated Mif2 and Mcd1/Scc1 when combined with a deletion of MCM21. Moreover, the loss of Cdc5 from the CEN chromatin contributes to defects in kinetochore integrity and reduction in CEN-associated Cse4. The cell cycle–regulated association of Cdc5 with Cse4 is essential for cell viability as constitutive association of Cdc5 with Cse4 at the kinetochore leads to growth defects. In summary, our results have defined a role for Cdc5-mediated Cse4 phosphorylation in faithful chromosome segregation.

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