scholarly journals Copaifera spp. oleoresins impair Toxoplasma gondii infection in both human trophoblastic cells and human placental explants

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Samuel Cota Teixeira ◽  
Guilherme de Souza ◽  
Bruna Cristina Borges ◽  
Thádia Evelyn de Araújo ◽  
Alessandra Monteiro Rosini ◽  
...  
Keyword(s):  
Direct Action ◽  
Congenital Toxoplasmosis ◽  
Host Cells ◽  
Bewo Cells ◽  
Trophoblastic Cells ◽  
Cycle Arrest ◽  
M Phase ◽  
Life Threatening ◽  
Parasite Replication ◽  
Toxoplasma Gondii Infection

Abstract The combination of pyrimethamine and sulfadiazine is the standard care in cases of congenital toxoplasmosis. However, therapy with these drugs is associated with severe and sometimes life-threatening side effects. The investigation of phytotherapeutic alternatives to treat parasitic diseases without acute toxicity is essential for the advancement of current therapeutic practices. The present study investigates the antiparasitic effects of oleoresins from different species of Copaifera genus against T. gondii. Oleoresins from C. reticulata, C. duckei, C. paupera, and C. pubiflora were used to treat human trophoblastic cells (BeWo cells) and human villous explants infected with T. gondii. Our results demonstrated that oleoresins were able to reduce T. gondii intracellular proliferation, adhesion, and invasion. We observed an irreversible concentration-dependent antiparasitic action in infected BeWo cells, as well as parasite cell cycle arrest in the S/M phase. The oleoresins altered the host cell environment by modulation of ROS, IL-6, and MIF production in BeWo cells. Also, Copaifera oleoresins reduced parasite replication and TNF-α release in villous explants. Anti-T. gondii effects triggered by the oleoresins are associated with immunomodulation of the host cells, as well as, direct action on parasites.

scholarly journals Biogenic Silver Nanoparticles Can Control Toxoplasma gondii Infection in Both Human Trophoblast Cells and Villous Explants

2021 ◽  
Vol 11 ◽  
Author(s):  
Idessania Nazareth Costa ◽  
Mayara Ribeiro ◽  
Priscila Silva Franco ◽  
Rafaela José da Silva ◽  
Thádia Evelyn de Araújo ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Toxoplasma Gondii ◽  
Chorionic Villus ◽  
Congenital Toxoplasmosis ◽  
Trophoblast Cells ◽  
Promising Alternative ◽  
Human Trophoblast ◽  
Biogenic Silver Nanoparticles ◽  
Bewo Cells ◽  
Toxoplasma Gondii Infection

The combination of sulfadiazine and pyrimethamine plus folinic acid is the conventional treatment for congenital toxoplasmosis. However, this classical treatment presents teratogenic effects and bone marrow suppression. In this sense, new therapeutic strategies are necessary to reduce these effects and improve the control of infection. In this context, biogenic silver nanoparticles (AgNp-Bio) appear as a promising alternative since they have antimicrobial, antiviral, and antiparasitic activity. The purpose of this study to investigate the action of AgNp-Bio in BeWo cells, HTR-8/SVneo cells and villous explants and its effects against Toxoplasma gondii infection. Both cells and villous explants were treated with different concentrations of AgNp-Bio or combination of sulfadiazine + pyrimethamine (SDZ + PYZ) in order to verify the viability. After, cells and villi were infected and treated with AgNp-Bio or SDZ + PYZ in different concentrations to ascertain the parasite proliferation and cytokine production profile. AgNp-Bio treatment did not reduce the cell viability and villous explants. Significant reduction was observed in parasite replication in both cells and villous explants treated with silver nanoparticles and classical treatment. The AgNp-Bio treatment increased of IL-4 and IL-10 by BeWo cells, while HTR8/SVneo cells produced macrophage migration inhibitory factor (MIF) and IL-4. In the presence of T. gondii, the treatment induced high levels of MIF production by BeWo cells and IL-6 by HTR8SV/neo. In villous explants, the AgNp-Bio treatment downregulated production of IL-4, IL-6, and IL-8 after infection. In conclusion, AgNp-Bio can decrease T. gondii infection in trophoblast cells and villous explants. Therefore, this treatment demonstrated the ability to reduce the T. gondii proliferation with induction of inflammatory mediators in the cells and independent of mediators in chorionic villus which we consider the use of AgNp-Bio promising in the treatment of toxoplasmosis in BeWo and HTR8/SVneo cell models and in chorionic villi.

scholarly journals Recent Advances in the Roles of Autophagy and Autophagy Proteins in Host Cells During Toxoplasma gondii Infection and Potential Therapeutic Implications

2021 ◽  
Vol 9 ◽  
Author(s):  
Carlos S. Subauste
Keyword(s):  
Toxoplasma Gondii ◽  
Parasitophorous Vacuole ◽  
Host Cells ◽  
Lysosomal Degradation ◽  
Therapeutic Implications ◽  
Obligate Intracellular ◽  
Recent Advances ◽  
Parasite Replication ◽  
Toxoplasma Gondii Infection ◽  
The Brain

Toxoplasma gondii is an obligate intracellular protozoan that can cause encephalitis and retinitis in humans. The success of T. gondii as a pathogen depends in part on its ability to form an intracellular niche (parasitophorous vacuole) that allows protection from lysosomal degradation and parasite replication. The parasitophorous vacuole can be targeted by autophagy or by autophagosome-independent processes triggered by autophagy proteins. However, T. gondii has developed many strategies to preserve the integrity of the parasitophorous vacuole. Here, we review the interaction between T. gondii, autophagy, and autophagy proteins and expand on recent advances in the field, including the importance of autophagy in the regulation of invasion of the brain and retina by the parasite. We discuss studies that have begun to explore the potential therapeutic applications of the knowledge gained thus far.

Alkylphospholipids are Signal Transduction Modulators with Potential for Anticancer Therapy

2019 ◽  
Vol 19 (1) ◽  
pp. 66-91 ◽  
Author(s):  
Ferda Kaleağasıoğlu ◽  
Maya M. Zaharieva ◽  
Spiro M. Konstantinov ◽  
Martin R. Berger
Keyword(s):  
Clinical Success ◽  
Phase Cell ◽  
Akt Phosphorylation ◽  
Cycle Arrest ◽  
M Phase ◽  
Mtor Phosphorylation ◽  
Antiviral Activities ◽  
Bone Marrow Sparing ◽  
Membrane Components ◽  
The Way

Background:Alkylphospholipids (APLs) are synthetically derived from cell membrane components, which they target and thus modify cellular signalling and cause diverse effects. This study reviews the mechanism of action of anticancer, antiprotozoal, antibacterial and antiviral activities of ALPs, as well as their clinical use.Methods:A literature search was used as the basis of this review.Results:ALPs target lipid rafts and alter phospholipase D and C signalling cascades, which in turn will modulate the PI3K/Akt/mTOR and RAS/RAF/MEK/ERK pathways. By feedback coupling, the SAPK/JNK signalling chain is also affected. These changes lead to a G2/M phase cell cycle arrest and subsequently induce programmed cell death. The available knowledge on inhibition of AKT phosphorylation, mTOR phosphorylation and Raf down-regulation renders ALPs as attractive candidates for modern medical treatment, which is based on individualized diagnosis and therapy. Corresponding to their unusual profile of activities, their side effects result from cholinomimetic activity mainly and focus on the gastrointestinal tract. These aspects together with their bone marrow sparing features render APCs well suited for modern combination therapy. Although the clinical success has been limited in cancer diseases so far, the use of miltefosine against leishmaniosis is leading the way to better understanding their optimized use.Conclusion:Recent synthetic programs generate congeners with the increased therapeutic ratio, liposomal formulations, as well as diapeutic (or theranostic) derivatives with optimized properties. It is anticipated that these innovative modifications will pave the way for the further successful development of ALPs.

scholarly journals The Antiproliferative Activity of Oxypeucedanin via Induction of G2/M Phase Cell Cycle Arrest and p53-Dependent MDM2/p21 Expression in Human Hepatoma Cells

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 501
Author(s):  
So Hyun Park ◽  
Ji-Young Hong ◽  
Hyen Joo Park ◽  
Sang Kook Lee
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Antiproliferative Activity ◽  
Hepatoma Cells ◽  
Phase Cell ◽  
Human Hepatoma Cells ◽  
Cycle Arrest ◽  
Growth Inhibitory Activity ◽  
M Phase

Oxypeucedanin (OPD), a furocoumarin compound from Angelica dahurica (Umbelliferae), exhibits potential antiproliferative activities in human cancer cells. However, the underlying molecular mechanisms of OPD as an anticancer agent in human hepatocellular cancer cells have not been fully elucidated. Therefore, the present study investigated the antiproliferative effect of OPD in SK-Hep-1 human hepatoma cells. OPD effectively inhibited the growth of SK-Hep-1 cells. Flow cytometric analysis revealed that OPD was able to induce G2/M phase cell cycle arrest in cells. The G2/M phase cell cycle arrest by OPD was associated with the downregulation of the checkpoint proteins cyclin B1, cyclin E, cdc2, and cdc25c, and the up-regulation of p-chk1 (Ser345) expression. The growth-inhibitory activity of OPD against hepatoma cells was found to be p53-dependent. The p53-expressing cells (SK-Hep-1 and HepG2) were sensitive, but p53-null cells (Hep3B) were insensitive to the antiproliferative activity of OPD. OPD also activated the expression of p53, and thus leading to the induction of MDM2 and p21, which indicates that the antiproliferative activity of OPD is in part correlated with the modulation of p53 in cancer cells. In addition, the combination of OPD with gemcitabine showed synergistic growth-inhibitory activity in SK-Hep-1 cells. These findings suggest that the anti-proliferative activity of OPD may be highly associated with the induction of G2/M phase cell cycle arrest and upregulation of the p53/MDM2/p21 axis in SK-HEP-1 hepatoma cells.

scholarly journals Steroid Glycosides Hyrcanoside and Deglucohyrcanoside: On Isolation, Structural Identification, and Anticancer Activity

Foods ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 136
Author(s):  
Silvie Rimpelová ◽  
Tomáš Zimmermann ◽  
Pavel B. Drašar ◽  
Bohumil Dolenský ◽  
Jiří Bejček ◽  
...  
Keyword(s):  
Drug Repositioning ◽  
Biological Activities ◽  
Cancer Therapeutics ◽  
Structural Identification ◽  
Induce Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Steroid Glycosides ◽  
In Silico Modeling ◽  
M Phase ◽  
Atpase Inhibition

Cardiac glycosides (CGs) represent a group of sundry compounds of natural origin. Most CGs are potent inhibitors of Na+/K+-ATPase, and some are routinely utilized in the treatment of various cardiac conditions. Biological activities of other lesser known CGs have not been fully explored yet. Interestingly, the anticancer potential of some CGs was revealed and thereby, some of these compounds are now being evaluated for drug repositioning. However, high systemic toxicity and low cancer cell selectivity of the clinically used CGs have severely limited their utilization in cancer treatment so far. Therefore, in this study, we have focused on two poorly described CGs: hyrcanoside and deglucohyrcanoside. We elaborated on their isolation, structural identification, and cytotoxicity evaluation in a panel of cancerous and noncancerous cell lines, and on their potential to induce cell cycle arrest in the G2/M phase. The activity of hyrcanoside and deglucohyrcanoside was compared to three other CGs: ouabain, digitoxin, and cymarin. Furthermore, by in silico modeling, interaction of these CGs with Na+/K+-ATPase was also studied. Hopefully, these compounds could serve not only as a research tool for Na+/K+-ATPase inhibition, but also as novel cancer therapeutics.

scholarly journals 1,3,4-Thiadiazoles Effectively Inhibit Proliferation of Toxoplasma gondii

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1053
Author(s):  
Lidia Węglińska ◽  
Adrian Bekier ◽  
Katarzyna Dzitko ◽  
Barbara Pacholczyk-Sienicka ◽  
Łukasz Albrecht ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Invasion ◽  
Direct Action ◽  
Human Fibroblasts ◽  
Imidazole Ring ◽  
Host Cells ◽  
In Vitro Assays ◽  
Host Cell Invasion

Congenital and acquired toxoplasmosis caused by the food- and water-born parasite Toxoplasma gondii (T. gondii) is one of the most prevalent zoonotic infection of global importance. T. gondii is an obligate intracellular parasite with limited capacity for extracellular survival, thus a successful, efficient and robust host cell invasion process is crucial for its survival, proliferation and transmission. In this study, we screened a series of novel 1,3,4-thiadiazole-2-halophenylamines functionalized at the C5 position with the imidazole ring (1b–12b) for their effects on T. gondii host cell invasion and proliferation. To achieve this goal, these compounds were initially subjected to in vitro assays to assess their cytotoxicity on human fibroblasts and then antiparasitic efficacy. Results showed that all of them compare favorably to control drugs sulfadiazine and trimethoprim in terms of T. gondii growth inhibition (IC50) and selectivity toward the parasite, expressed as selectivity index (SI). Subsequently, the most potent of them with meta-fluoro 2b, meta-chloro 5b, meta-bromo 8b, meta-iodo 11b and para-iodo 12b substitution were tested for their efficacy in inhibition of tachyzoites invasion and subsequent proliferation by direct action on established intracellular infection. All the compounds significantly inhibited the parasite invasion and intracellular proliferation via direct action on both tachyzoites and parasitophorous vacuoles formation. The most effective was para-iodo derivative 12b that caused reduction in the percentage of infected host cells by 44% and number of tachyzoites per vacuole by 93% compared to non-treated host cells. Collectively, these studies indicate that 1,3,4-thiadiazoles 1b–12b, especially 12b with IC50 of 4.70 µg/mL and SI of 20.89, could be considered as early hit compounds for future design and synthesis of anti-Toxoplasma agents that effectively and selectively block the invasion and subsequent proliferation of T. gondii into host cells.

Design, synthesis of novel quinazolinone-based oxobutanonitrile derivatives as antiproliferative agents targeting human breast cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Omaima Mohamed AboulWafa ◽  
Hoda Mohamed Gamal El-Din Daabees ◽  
Eman Salah Ezz-ElDien
Keyword(s):  
Breast Cancer ◽  
Binding Affinities ◽  
Caspase 9 ◽  
Design Synthesis ◽  
Egfr Inhibition ◽  
Cycle Arrest ◽  
M Phase ◽  
Quinazolinone Derivatives ◽  
Mcf 7

Background: Breast cancer (BC) is among the leading causes of death among women worldwide. Medical interest has focused on quinazolinone derivatives approved and utilized in antitumor medications. Objective: Novel quinazolinone-based oxobutanonitrile derivatives were designed, synthesized, and screened for in vitro anti-BC activity. Methods: The antiproliferative activities were determined using MTT assay against MCF-7 and MDA-MB-231 cell lines. EGFR, ARO, and caspase-9 enzymes were selected to explore the mechanism of action of the most potent compounds. Results: Tested compounds showed better EGFRIs than ARIs. In addition, significant overexpression in caspase-9 level in treated MCF-7 breast cell line samples was observed with the most active compounds. The thienyl derivative 5 induced the greatest activation in caspase-9 level in treated MCF-7 breast cancer samples. The o-tolylhydrazone 3b, exhibiting promising ARO inhibition and weak EGFR inhibition, produced a noticeable high overexpression of caspase-9 and showed pre-G1 apoptosis and cell cycle arrest at G2/M phase for MCF-7 cells and at S-phase for MDA-MB-231 cells. Docking results revealed that 3b, elicited binding affinities to ARO comparable to those of letrozole. Conclusion: The obtained results support the therapeutic importance of some of these compounds as anti-BC agents in light of the simple methodology used for their synthesis. Their design offered a way for the optimization and development of apoptotic quinazolinone-based ARO and EGFR inhibitors.

N-(3'-acetyl-8-nitro-2,3-dihydro-1H,3'H-spiro[quinoline-4,2'-[1,3,4]thiadiazol]-5'-yl) acetamides Induced Cell death in MCF-7 cells via G2/M Phase Cell Cycle Arrest

2022 ◽  
Author(s):  
Selvaraj Shyamsivappan ◽  
Raju Vivek ◽  
Thangaraj Suresh ◽  
Palanivel Naveen ◽  
Kaviyarasu Adhigaman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Spectroscopic Studies ◽  
Phase Cell ◽  
X Ray ◽  
Cycle Arrest ◽  
M Phase ◽  
Mcf 7

A progression of new N-(3'-acetyl-8-nitro-2,3-dihydro-1H,3'H-spiro[quinoline-4,2'-[1,3,4]thiadiazol]-5'-yl) acetamide derivatives were synthesized from potent 8-nitro quinoline-thiosemicarbazones. The synthesized compounds were characterized by different spectroscopic studies and single X-ray crystallographic studies. The compounds were...

Microtubules, but not actin filaments, drive daughter cell budding and cell division in Toxoplasma gondii

2000 ◽  
Vol 113 (7) ◽  
pp. 1241-1254 ◽  
Author(s):  
M.K. Shaw ◽  
H.L. Compton ◽  
D.S. Roos ◽  
L.G. Tilney
Keyword(s):  
Toxoplasma Gondii ◽  
Actin Cytoskeleton ◽  
Daughter Cell ◽  
Protozoan Parasite ◽  
Host Cells ◽  
Actin Dynamics ◽  
Residual Body ◽  
Cell Organelles ◽  
Infection Period ◽  
Parasite Replication

We have used drugs to examine the role(s) of the actin and microtubule cytoskeletons in the intracellular growth and replication of the intracellular protozoan parasite, Toxoplasma gondii. By using a 5 minute infection period and adding the drugs shortly after entry we can treat parasites at the start of intracellular development and 6–8 hours prior to the onset of daughter cell budding. Using this approach we found, somewhat surprisingly, that reagents that perturb the actin cytoskeleton in different ways (cytochalasin D, latrunculin A and jasplakinolide) had little effect on parasite replication although they had the expected effects on the host cells. These actin inhibitors did, however, disrupt the orderly turnover of the mother cell organelles leading to the formation of a large residual body at the posterior end of each pair of budding parasites. Treating established parasite cultures with the actin inhibitors blocked ionophore-induced egression of tachyzoites from the host cells, demonstrating that intracellular parasites were susceptible to the effects of these inhibitors. In contrast, the anti-microtubule drugs oryzalin and taxol, and to a much lesser extent nocodazole, which affect microtubule dynamics in different ways, blocked parasite replication by disrupting the normal assembly of the apical conoid and the microtubule inner membrane complex (IMC) in the budding daughter parasites. Centrosome replication and assembly of intranuclear spindles, however, occurred normally. Thus, daughter cell budding per se is dependent primarily on the parasite microtubule system and does not require a dynamic actin cytoskeleton, although disruption of actin dynamics causes problems in the turnover of parasite organelles.

Sign in / Sign up

Export Citation Format

Share Document