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1.
Braz. J. Pharm. Sci. (Online) ; 60: e23380, 2024. graf
Article Dans Anglais | LILACS | ID: biblio-1533983

Résumé

Abstract Glioblastoma multiforme is a tumor of the central nervous system. Focal Adhesion Kinase (FAK) and αB-crystalline are two proteins involved in glioblastoma development. In this study, we investigated whether the FAK/αB-crystalline interaction is important for glioblastoma cells, we aimed to investigate the interaction of these two proteins in the glioblastoma multiforme cell line U87-MG. Two peptides named FP01 peptide (derived from αB-crystalline) and FP02 peptide (derived from FAK) were synthesized for this study. Treatment of U87-MG with the peptides FP01 and FP02 in the concentration at 50 µM reduced the viability cellular to around 41% and 51%, respectively. Morphological alterations in the cells treated with the peptides when compared to the control were observed. This study suggests that the interaction between FAK and αB-crystalline is important for the viability of glioblastoma cells


Sujets)
Peptides/effets indésirables , Cellules/classification , Glioblastome/anatomopathologie , Focal adhesion protein-tyrosine kinases/effets indésirables , Tumeurs/anatomopathologie , Lignée cellulaire/classification , Système nerveux central/malformations
2.
Braz. J. Pharm. Sci. (Online) ; 59: e23075, 2023. graf
Article Dans Anglais | LILACS | ID: biblio-1505836

Résumé

Abstract Focal Adhesion Kinase (FAK) protein participates in proliferation, migration, cell survival, and apoptosis process. It has been described as overexpressed in several neoplasms being a promising target for therapy. BCR-ABL negative chronic Myeloproliferative Neoplasms (MPN) are clonal disorders characterized by the excess of proliferation and apoptosis resistance. The identification of the acquired JAK2 V617F mutation in MPN patients allowed a better understanding of pathogenesis. However, there is still no pharmacological treatment that leads all patients to molecular remission, justifying new studies. The present study aimed to evaluate FAK involvement in the viability and apoptosis of HEL and SET-2 cells, both JAK2 V617F positive cell lines. The FAK inhibitor PF 562,271 was used. Cell viability was determined using MTT assay and apoptosis verified by cleaved PARP, cleaved Caspase 3 and Annexin-V/PI staining detection. FAK inhibition significantly reduced HEL and SET-2 cells viability and induced apoptosis. Considering the role of JAK/STAT pathway in MPN, further investigation of FAK participation in the MPN cells proliferation and apoptosis resistance, as well as possible crosstalk between JAK and FAK and downstream pathways may contribute to the knowledge of MPN pathophysiology, the discovery of new molecular targets, and JAK inhibitors resistance mechanisms.


Sujets)
Apoptose , Focal adhesion protein-tyrosine kinases/analyse , Kinase Janus-2/effets indésirables , Patients/classification , Lignée cellulaire/classification , Tumeurs/anatomopathologie
3.
Braz. J. Pharm. Sci. (Online) ; 58: e19221, 2022. tab, graf
Article Dans Anglais | LILACS | ID: biblio-1374557

Résumé

Abstract The purpose of the current work was to assess a possible role of cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) in the metabolic activation of 2,6-dimethylaniline (2,6-DMA) and also clarify the function of DNA repair in affecting the ultimate mutagenic potency. Two cell lines, nucleotide excision repair (NER)-deficient 5P3NAT2 and proficient 5P3NAT2R9 both expressing CYP1A2 and NAT2, were treated with 2,6-DMA for 48 h or its metabolites for 1 h. Cell survival determined by trypan blue exclusion and MTT assays, and 8-azaadenine-resistant mutants at the adenine phosphoribosyltransferase (aprt) gene locus were evaluated. 5P3NAT2 and 5P3NAT2R9 cells treated with 2,6-DMA and its metabolites showed a dose-dependent increase in cytotoxicity and mutant fraction; N-OH-2,6-DMA and 2,6-DMAP in serum-free α-minimal essential medium (MEM) are more potent than 2,6-DMA in complete MEM. 5P3NAT2 cells was more sensitive to the cytotoxic and mutagenic action than 5P3NAT2R9 cells. H2DCFH-DA assay showed dose-dependent ROS production under 2,6- DMAP treatment. These findings indicate that the genotoxic effects of 2,6-DMA are mediated by CYP1A2 activation via N-hydroxylation and the subsequent esterification by the phase II conjugation enzyme NAT2, and through the generation of ROS by hydroxylamine and/or aminophenol metabolites. NER status is also an important contributor


Sujets)
Cellules/classification , Cytochrome P-450 CYP1A2/analyse , Génotoxicité , Lignée cellulaire/classification , Hydroxylamine/agonistes , Réparation de l'ADN
4.
Braz. J. Pharm. Sci. (Online) ; 58: e19194, 2022. tab, graf
Article Dans Anglais | LILACS | ID: biblio-1383971

Résumé

Abstract Increasing biological activity and phytochemical investigations on Eryngium species showed its potential as pharmaceutical approach. Eryngium kotschyi Boiss. is one of the species of Eryngium genus and is endemic to Turkey. It is known that this plant is traditionally used in the South-western part of Turkey for the treatment of various diseases. This study focuses on cytotoxic activities of methanol extract and ethyl acetate, n-butanol and water sub-extracts from E. kotschyi in A549, COLO 205 and MDA-MB-231 cell lines by Sulforhodamin B assay and qualitative and quantitative determination of phytochemical constituents in active extract by LC-MS/MS. From the result of the study, it was seen that E. kotschyi ethyl acetate (EKE) sub-extract showed the strongest cytotoxic effect with the low IC50 values (50.00; 31.96 and 22.26 µg/mL in A549; COLO 205 and MDA-MB-231 cells at 48 h, respectively). Preliminary examination of the mass spectrums revealed the presence of 15 phytochemical compounds in active sub-extract and 7 of them was quantified. According to quantitative analyses the main compounds of EKE sub-extract were rosmarinic acid (485.603 µg/mgextract), chlorogenic acid (62.355 µg/mgextract) and caffeic acid (59.266 µg/mgextract). Moreover, this preliminary study on inhibitory activity of EKE sub-extract suggests further toxicologic investigations and detailed investigation on cytotoxic effect of various combinations of determined compounds


Sujets)
Turquie/ethnologie , Cellules/métabolisme , Eryngium/anatomie et histologie , Composés phytochimiques/effets indésirables , Préparations pharmaceutiques/administration et posologie , Lignée cellulaire/classification , Cellules A549/métabolisme , Acétates/administration et posologie
5.
Braz. J. Pharm. Sci. (Online) ; 58: e191072, 2022. graf
Article Dans Anglais | LILACS | ID: biblio-1383975

Résumé

Abstract Thymoquinone (TQ) has shown hepatoprotective effects in various experimental studies. We aimed to investigate the possible beneficial effects of TQ regarding its prevention of alpha-amanitin induced hepatotoxicity in human C3A hepatocytes. After administering alpha-amanitin in a concentrations of 1 and 10µg/mL on the cells in a hepatocyte cell line, TQ was administered in various concentrations (10, 5, 1, 0.5, 0.1, 0.05, 0.01, 0.005 µg/mL). The MTT test was used to determine cell viability. For the groups given only TQ at various concentrations, the cell viability rates at 48 hours post-administration were found at 82.6, 98.3, 102.1, 102.5, 99.4, 99.4, 101.9 and 106.3%, respectively. For the group with 1μg/mL alpha-amanitin and various TQ concentrations, the cell viability rates were found at 74.6, 88.5, 87.4, 88.7, 85.7, 86.8, 88.4, and 92.9%, respectively. For the group with 10μg/mL alpha-amanitin and various TQ concentrations, the cell viability rates for each TQ subgroup were found at 65.2, 79.2, 81.4, 81.1, 81.8, 81.8, 82.2 and 91.9%, respectively. Our study is the first in vitro study that investigates TQ's effects on alpha-amanitin induced hepatotoxicity. Although TQ had beneficial effect in low doses did not significantly increase cell viability in liver damage due to alpha-amanitin toxicity.


Sujets)
Lignée cellulaire/classification , Techniques in vitro/méthodes , alpha-Amanitine/administration et posologie , Foie/physiopathologie
6.
Braz. J. Pharm. Sci. (Online) ; 56: e18411, 2020. tab, graf
Article Dans Anglais | LILACS | ID: biblio-1132049

Résumé

Antimicrobial and antitumor activities of resveratrol, a compound found mainly in grapes, have already been demonstrated. However, its low bioavailability is a limiting factor for therapeutic application. Polymeric micelles can be an approach to solve this problem since they can encapsulate hydrophobic substances. We developed and characterized micellar formulations containing resveratrol and evaluated their cytotoxic and antimicrobial effects. The formulations were prepared by the cold dispersion method with different concentrations of F127 (5 or 10% w/w) and resveratrol (500 or 5000 µM). The formulations were characterized according to size, polydispersity index, pH, encapsulation rate and in vitro release. Cytotoxic effect was evaluated on a bladder cancer cell line and antimicrobial effect was evaluated on E. coli, S. aureus and C. albicans. One of the formulations (10% w/w of F127 and 5000 µM of resveratrol) was a monodispersed solution with high encapsulation rate, thus it was chosen for the cytotoxicity and antimicrobial assays. MS- 10+RES-3 was able to preserve the antimicrobial and cytotoxic activity of resveratrol. This is the first study that evaluated antimicrobial potential and cytotoxicity of micelles containing resveratrol on bladder cancer cells and the results showed that micellar nanostructures could ensure the maintenance of the biological activity of resveratrol.


Sujets)
Tumeurs de la vessie urinaire , Cellules , Resvératrol/analyse , Tumeurs/anatomopathologie , Solutions/administration et posologie , Techniques in vitro/instrumentation , Lignée cellulaire/classification , Vitis/classification , Concentration en ions d'hydrogène , Micelles
7.
Rev. microbiol ; 24(1): 71-2, mar. 1993. ilus
Article Dans Portugais | LILACS | ID: lil-280146

Résumé

Foi isolada uma nova linhagem de Saccharomyces cerevisuiae 337, de usina de cana de açucar, que apresentou ativudade "Killer" semelhante ao fenótipo K.A eletroforese em gel de agarose mostrou que a linhagem S.cerevisiae 337 possui dois ds-RNAs. A atividade "killer" da linhagem foi comparada com a levedura padräo"Killer" K


Sujets)
Saccharomyces cerevisiae/croissance et développement , Levures/classification , Levures/composition chimique , Lignée cellulaire/cytologie , Lignée cellulaire/classification , Électrophorèse , Techniques in vitro , Plasmides/classification
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