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1.
Int J Mol Sci ; 23(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36555562

RESUMO

The harmful effects of silver nanoparticles (AgNPs) have been confirmed in many organisms, but the mechanism of their toxicity is not yet fully understood. In biological systems, AgNPs tend to aggregate and dissolve, so they are often stabilized by coatings that influence their physico-chemical properties. In this study, the effects of AgNPs with different coatings [polyvinylpyrrolidone (PVP) and cetyltrimethylammonium bromide (CTAB)] on oxidative stress appearance and proteome changes in tobacco (Nicotiana tabacum) seedlings have been examined. To discriminate between the nanoparticulate Ag form from the ionic one, the treatments with AgNO3, a source of Ag+ ions, were also included. Ag uptake and accumulation were found to be similarly effective upon exposure to all treatment types, although positively charged AgNP-CTAB showed less stability and a generally stronger impact on the investigated parameters in comparison with more stable and negatively charged AgNP-PVP and ionic silver (AgNO3). Both AgNP treatments induced reactive oxygen species (ROS) formation and increased the expression of proteins involved in antioxidant defense, confirming oxidative stress as an important mechanism of AgNP phytotoxicity. However, the mechanism of seedling responses differed depending on the type of AgNP used. The highest AgNP-CTAB concentration and CTAB coating resulted in increased H2O2 content and significant damage to lipids, proteins and DNA molecules, as well as a strong activation of antioxidant enzymes, especially CAT and APX. On the other hand, AgNP-PVP and AgNO3 treatments induced the nonenzymatic antioxidants by significantly increasing the proline and GSH content. Exposure to AgNP-CTAB also resulted in more noticeable changes in the expression of proteins belonging to the defense and stress response, carbohydrate and energy metabolism and storage protein categories in comparison to AgNP-PVP and AgNO3. Cysteine addition significantly reduced the effects of AgNP-PVP and AgNO3 for the majority of investigated parameters, indicating that AgNP-PVP toxicity mostly derives from released Ag+ ions. AgNP-CTAB effects, however, were not alleviated by cysteine addition, suggesting that their toxicity derives from the intrinsic properties of the nanoparticles and the coating itself.


Assuntos
Antioxidantes , Nanopartículas Metálicas , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Nicotiana/metabolismo , Plântula/metabolismo , Prata/química , Proteômica , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química , Cetrimônio/farmacologia , Cisteína/metabolismo , Peróxido de Hidrogênio/metabolismo , Nitrato de Prata/toxicidade
2.
Nanomedicine (Lond) ; 17(22): 1663-1676, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36515357

RESUMO

Aim: To investigate the antifungal activity of two different functionalized gold nanoparticles (AuNP), those stabilized with cetyltrimethylammonium bromide and those conjugated with cysteine, and their effects on the architecture of Candida tropicalis biofilms. Materials & methods: Biofilms were studied by crystal violet binding assay and scanning electron microscopy. We investigated the effects of AuNPs on reactive oxygen species, reactive nitrogen intermediates and enzymatic and nonenzymatic antioxidant defenses. Results/Conclusion: The fungicidal activity and cellular stress of both AuNPs affected biofilm growth through accumulation of reactive oxygen species and reactive nitrogen intermediates. However, cetyltrimethylammonium bromide-stabilized AuNPs revealed a higher redox imbalance. We correlated, for the first time, AuNP effects with the redox imbalance and alterations in the architecture of C. tropicalis biofilms.


Biofilms are at least 100­1000-times more resistant to the effects of antimicrobial agents compared with planktonic cells, and nanoparticles have emerged to provide new approaches to improve the safety and efficacy of antimicrobial therapy. The aim of this work was to investigate the antifungal activity with two different functionalized gold nanoparticles. A significant reduction of Candida tropicalis biofilms with alterations in surface topography and architecture was observed, and the oxidative and nitrosative stress affected the biofilms. To the best of our knowledge, this is the first study that attempts to correlate the antibiofilm effects of gold nanoparticles on the redox imbalance against biofilms. These compounds could be an alternative to fungal biofilms infections treatments, applied specifically in biological and medical fields.


Assuntos
Candida tropicalis , Nanopartículas Metálicas , Ouro/farmacologia , Cetrimônio/farmacologia , Antifúngicos/farmacologia , Biofilmes , Testes de Sensibilidade Microbiana
3.
Sci Rep ; 12(1): 2825, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35181714

RESUMO

The high quality, yield and purity total RNA samples are essential for molecular experiments. However, harvesting high quality RNA in Lilium davidii var. unicolor is a great challenge due to its polysaccharides, polyphenols and other secondary metabolites. In this study, different RNA extraction methods, namely TRIzol method, the modified TRIzol method, Kit method and cetyltrimethylammonium bromide (CTAB) method were employed to obtain total RNA from different tissues in L. davidii var. unicolor. A Nano drop spectrophotometer and 1% agarose gel electrophoresis were used to detect the RNA quality and integrity. Compared with TRIzol, Kit and CTAB methods, the modified TRIzol method obtained higher RNA concentrations from different tissues and the A260/A280 ratios of RNA samples were ranged from 1.97 to 2.27. Thus, the modified TRIzol method was shown to be the most effective RNA extraction protocol in acquiring RNA with high concentrations. Furthermore, the RNA samples isolated by the modified TRIzol and Kit methods were intact, whereas different degrees of degradation happened within RNA samples isolated by the TRIzol and CTAB methods. In addition, the modified TRIzol method could also isolate high-quality RNA from other edible lily bulbs. Taken together, the modified TRIzol method is an efficient method for total RNA isolation from L. davidii var. unicolor.


Assuntos
Lilium/química , RNA de Plantas/isolamento & purificação , Cetrimônio/farmacologia , Guanidinas/farmacologia , Fenóis/farmacologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Polifenóis/farmacologia , RNA de Plantas/química
4.
Anticancer Res ; 41(12): 6095-6104, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34848464

RESUMO

BACKGROUND/AIM: This study investigated the anti-metastatic effects of cetyltrimethylammonium bromide (CTAB) on tongue squamous cell carcinoma (TSCC) SCC4 cells. MATERIALS AND METHODS: Cell morphology, viability, cell cycle distribution, adhesion, migration, invasion and the expression levels of associated proteins were examined using microscopy, WST-1, wound-healing, Boyden chamber assays, and western blotting, respectively. RESULTS: CTAB significantly affected SCC4 cell morphology from spindle-shaped to cobblestone-shaped and resulted in loss of adherence. CTAB significantly inhibited cell adhesion, migration, and invasion of SCC4 cells, independent of cell viability. CTAB reduced expression of matrix metalloproteinases (MMPs) such as MMP3, MMP7, and MMP14 in a concentration-dependent manner, while it increased expression of tissue inhibitors of metalloproteinase 3 (TIMP3). In addition, CTAB reduced the phosphorylation of mothers against decapentaplegic homolog 2/3 (Smad2/3) proteins, which mediated CTAB-inhibited migration and invasion in SCC4 cells. These effects were reversed by TGF-ß1. CONCLUSION: CTAB attenuates the mesenchymal characteristics through upregulation of TIMP3 by inhibiting the canonical TGF-ß/Smad/miR-181b/TIMP3 signaling involved in extracellular matrix remodeling in SCC4 cells and might be a promising anti-metastatic therapeutic agent for TSCC.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Cetrimônio/uso terapêutico , Proteína Smad2/metabolismo , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Neoplasias da Língua/tratamento farmacológico , Fator de Crescimento Transformador beta1/metabolismo , Linhagem Celular Tumoral , Cetrimônio/farmacologia , Humanos , Transdução de Sinais , Transfecção
5.
Anticancer Res ; 41(8): 3789-3799, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281838

RESUMO

BACKGROUND/AIM: Cetyltrimethylammonium bromide (CTAB), a quaternary ammonium surfactant, was shown to have antitumor effects in a cellular mode of head and neck squamous cell carcinoma (HNSCC), modulating apoptotic and cytotoxic processes. However, the mechanisms by which CTAB exerts its effects against the epithelial- mesenchymal transition in HNSCC remain poorly understood. In the present study, we investigated whether CTAB inhibits cellular mobility and invasiveness of hypopharyngeal squamous cell carcinoma (HPSCC) cells. MATERIALS AND METHODS: WST-1, cell-cycle phase distribution, and wound healing, as well as transwell assays were conducted. Changes in protein expression patterns and related signaling pathways involved in effects of CTAB on HPSCC cell lines were evaluated by western blotting. RESULTS: Treatment of human HPSCC cell lines with CTAB significantly altered their morphology from spindle-like to cobblestone-like by diminishing mesenchymal-like phenotypic characteristics. CTAB also hindered cell functional properties, including migration and invasion, independently of cell viability. In addition, western blot results demonstrated that treatment with CTAB reduced expression of mesenchymal markers. Further investigation showed that CTAB treatment suppressed the phosphorylation of extracellular-regulated kinase 1/2, mechanistic target of rapamycin kinase and AKT serine/threonine kinase 1. CTAB also repressed the expression and phosphorylation levels of epidermal growth factor receptor (EGFR) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and the partial restoration of mesenchymal phenotype by EGF addition confirmed that CTAB inhibited migration and invasion in HPSCC cells by blocking the EGFR signaling pathway. CONCLUSION: Our results suggest that CTAB is involved in the suppression of EGFR-mediated mesenchymal phenotype and the molecular mechanism by which CTAB obstructs HPSCC cell metastasis may represent a promising strategy for use in HPSCC treatment.


Assuntos
Cetrimônio/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Antineoplásicos/farmacologia , Adesão Celular/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/fisiologia , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Serina-Treonina Quinases TOR/metabolismo
6.
Sci Rep ; 11(1): 10798, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031478

RESUMO

Two synthetic approaches were explored for modification of the polyolefins polyethylene/polypropylene (PE/PP) to form contact-active nonwoven materials. In the first approach, polymer surfaces were activated by O2-free air-ozonolysis, and then the active agent (trimethoxysilyl) propyl-octadecyl-dimethyl-ammonium chloride (C18-TSA) was covalently bound. In the second approach, the active agent was directly conjugated to the commercial 'finishing' that was then applied to the polymer. The chemical, physical and microscopic properties of the modified polymers were comprehensively studied, and their active site density was quantified by fluorescein sodium salt-cetyltrimethylammonium chloride reaction. The antimicrobial activity of the prepared nonwovens against Bacillus subtilis (Gram-positive) and Salmonella enterica (Gram-negative), and their stability at various pHs and temperatures were examined. The two approaches conferred antimicrobial properties to the modified polymers and demonstrated stable linkage of C18-TSA. However, the performance of the nonwovens formed by the first approach was superior. The study suggests two feasible and safe pathways for the modification of polyolefins to form contact-active nonwoven materials that can be further applied in various fields, such as hygiene products, medical fabrics, sanitizing wipes, and more.


Assuntos
Antibacterianos/síntese química , Bacillus subtilis/crescimento & desenvolvimento , Polietilenos/síntese química , Polipropilenos/síntese química , Salmonella enterica/crescimento & desenvolvimento , Antibacterianos/química , Antibacterianos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Cetrimônio/síntese química , Cetrimônio/química , Cetrimônio/farmacologia , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Ozônio/química , Polietilenos/química , Polietilenos/farmacologia , Polipropilenos/química , Polipropilenos/farmacologia , Compostos de Amônio Quaternário , Salmonella enterica/efeitos dos fármacos , Propriedades de Superfície , Temperatura
7.
Int J Oncol ; 59(1)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34013357

RESUMO

Osteosarcoma (OS) metastasis and recurrence and multidrug resistance are three major obstacles in the clinic. New highly effective and low toxicity drugs for osteosarcoma are needed. The antitumoral efficacy of cetrimonium bromide (CTAB), a quaternary ammonium compound, is gradually being investigated. The aim of the present study was to investigate the effects of CTAB on OS cells and the underlying mechanisms. CTAB inhibited the proliferation of osteosarcoma cells in a concentration­ and time­dependent manner, resulting in cell cycle arrest in G1 phase. CTAB also suppressed the migration and invasion of HOS and MG63 cells at a low concentration without inhibiting the growth of human osteoblasts. Moreover, CTAB promoted caspase­mediated apoptosis of osteosarcoma cells through the PI3K/AKT cascade, and this effect was accompanied by obvious mitochondrial toxicity. In vivo, CTAB inhibited OS proliferation without inducing organ toxicity. In conclusion, this study reveals that CTAB has an inhibitory effect on OS by suppressing proliferation and metastasis and inducing apoptosis through the PI3K/AKT signaling pathway and identifies CTAB as a potential therapeutic drug.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Cetrimônio/farmacologia , Osteossarcoma/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Antinematódeos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Nus , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Int J Nanomedicine ; 16: 2789-2801, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33880024

RESUMO

OBJECTIVE: Gold nanorods (AuNRs) show great potential for versatile biomedical applications, such as stem cell therapy and bone tissue engineering. However, as an indispensable shape-directing agent for the growth of AuNRs, cetyltrimethylammonium bromide (CTAB) is not optimal for biological studies because it forms a cytotoxic bilayer on the AuNR surface, which interferes with the interactions with biological cells. METHODS: Citrate-stabilized AuNRs with various aspect-ratios (Cit-NRI, Cit-NRII, and Cit-NRIII) were prepared by the combination of end-selective etching and poly(sodium 4-styrenesulfonate)-assisted ligand exchange method. Their effects on osteogenic differentiation of the pre-osteoblastic cell line (MC3T3-E1), rat bone marrow mesenchymal stem cells (rBMSCs), and human periodontal ligament progenitor cells (PDLPs) have been investigated. Potential signaling pathway of citrate-stabilized AuNRs-induced osteogenic effects was also investigated. RESULTS: The experimental results showed that citrate-stabilized AuNRs have superior biocompatibility and undergo aspect-ratio-dependent osteogenic differentiation via expression of osteogenic marker genes, alkaline phosphatase (ALP) activity and formation of mineralized nodule. Furthermore, Wnt/ß-catenin signaling pathway might provide a potential explanation for the citrate-stabilized AuNRs-mediated osteogenic differentiation. CONCLUSION: These findings revealed that citrate-stabilized AuNRs with great biocompatibility could regulate the osteogenic differentiation of multiple cell types through Wnt/ß-catenin signaling pathway, which promote innovative AuNRs in the field of tissue engineering and other biomedical applications.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Ácido Cítrico/farmacologia , Ouro/farmacologia , Nanotubos/química , Osteogênese/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Células Cultivadas , Cetrimônio/farmacologia , Endocitose/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Nanotubos/ultraestrutura , Osteogênese/genética , Ligamento Periodontal/citologia , Ratos , Tiazolidinas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos
9.
J Microbiol Biotechnol ; 31(3): 439-446, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33526753

RESUMO

Quercus infectoria (nutgall) has been reported to possess antimicrobial activities against a wide range of pathogens. Nevertheless, the biofilm removal effect of nutgall extract has not been widely investigated. In this study, we therefore evaluated the effect of nutgall extract in combination with cetrimonium bromide (CTAB) against preformed biofilm of Salmonella Typhimurium on polypropylene (PP) and stainless steel (SS) coupons in comparison with other sanitizers. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of nutgall extract and surfactants (CTAB and sodium dodecyl sulfate; SDS) were assessed. CTAB showed a more efficient antimicrobial activity than SDS and was selected to use in combination with nutgall extract for removing biofilm. To determine the biofilm removal efficacy, the PP and SS coupons were individually submerged in 2x MBC of nutgall extract (256 mg/ml) + 2x MBC of CTAB (2.5 mg/ml), nutgall extract alone (256 mg/ml), CTAB alone (2.5 mg/ml), distilled water, and 100 ppm sodium hypochlorite for 5, 15, and 30 min. The remaining sessile cells in biofilm were determined. Overall, the greatest biofilm removal efficacy was observed with nutgall extract + CTAB; the biofilm removal efficacy of sanitizers tended to increase with the exposure time. The SEM analysis demonstrated that S. Typhimurium biofilm on PP and SS coupons after exposure to nutgall extract + CTAB for 30 min displayed morphological alterations with wrinkles. This study suggests nutgall extract + CTAB may be an alternative to commonly used sanitizers to remove biofilm from food contact surfaces in the food industry and household.


Assuntos
Biofilmes/efeitos dos fármacos , Cetrimônio/farmacologia , Extratos Vegetais/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Dodecilsulfato de Sódio/farmacologia , Contagem de Colônia Microbiana , Descontaminação/métodos , Microbiologia de Alimentos , Testes de Sensibilidade Microbiana , Tumores de Planta , Polipropilenos , Quercus/química , Aço Inoxidável , Tensoativos/farmacologia
10.
Anticancer Res ; 40(9): 5059-5069, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878794

RESUMO

BACKGROUND/AIM: Liver cancer is the fourth leading cause of cancer-related mortality globally, of which hepatocellular carcinoma (HCC) accounts for 85-90% of total primary liver cancer. A drug shortage for HCC therapy triggered us to screen the small-molecule database with a high-throughput cellular screening system. Herein, we examined whether cetyltrimethylammonium bromide (CTAB) inhibits cellular mobility and invasiveness of Mahlavu HCC cells. MATERIALS AND METHODS: The effects of CTAB on cell viability were assessed using WST-1 assay, cell-cycle distribution using flow cytometric analysis, migration/invasion using woundhealing and transwell assays, and associated protein levels using western blotting. RESULTS: Treatment of Mahlavu cells with CTAB transformed its mesenchymal spindle-like morphology. In addition, CTAB exerted inhibitory effects on the migration and invasion of Mahlavu cells dose-dependently. CTAB also reduced the protein levels of matrix metalloproteinase-2 (MMP2), MMP9, RAC family small GTPase 1, SNAIL family transcriptional repressor 1 (SNAI1), SNAI2, TWIST family basic helix-loop-helix transcription factor 1 (TWIST1), vimentin, N-cadherin, phospho-fibroblast growth factor (FGF) receptor, phospho-phosphoinositide 3-kinase, phospho-v-Akt murine thymoma viral oncogene and phospho-signal transducer and activator of transcription 3 but increased the protein levels of tissue inhibitor of metalloproteinases-1/2 and E-cadherin. Rescue experiments proved that CTAB induced mesenchymal-epithelial transition in Mahlavu cells and this was significantly dose-dependently mitigated by basic FGF. CONCLUSION: CTAB suppressed the migration and invasion of Mahlavu cells through inhibition of the FGF signaling pathway. CTAB seems to be a potential agent for preventing metastasis of hepatic cancer.


Assuntos
Antineoplásicos/farmacologia , Cetrimônio/farmacologia , Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Biomarcadores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Anticancer Res ; 40(8): 4513-4522, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727781

RESUMO

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) arises from hepatocytes, and is the most frequently occurring malignancy of primary liver cancer. In this study, we investigated the anti-metastatic effects of the quaternary ammonium compound, cetyltrimethylammonium bromide (CTAB), on HA22T/VGH HCC cells. MATERIALS AND METHODS: According to our preliminary data, the effect of CTAB on cell cycle distribution, migration, invasion and the associated protein levels was examined using flow cytometry, wound-healing migration, Matrigel transwell invasion assay and western blotting under sub-lethal concentrations. RESULTS: CTAB treatment of HA22T/VGH cells casued dose-dependent mesenchymal-epithelial transition (MET)-like changes and impaired migration and invasion capabilities. In addition, CTAB reduced the levels of metastasis-related proteins including c-Met, phosphoinositide 3-kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), Twist, N-cadherin, and Vimentin. Moreover, pretreatment with hepatocyte growth factor (HGF) rescued CTAB-mediated effects. CONCLUSION: CTAB exhibited potent anti-EMT and anti-metastatic activities through the inhibition of migration and invasion of HA22T/VGH cells. CTAB interrupted the mesenchymal characteristics of HA22T/VGH cells, which were significantly alleviated by HGF in a dose-dependent manner. CTAB has the potential to evolve as a therapeutic agent for HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Cetrimônio/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Serina-Treonina Quinases TOR/metabolismo
12.
Nanoscale ; 12(7): 4328-4333, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32043517

RESUMO

Biofilms that form on reusable medical devices are a cause of hospital acquired infections; however, sanitization of biofilms is a challenge due to their dense extracellular matrix. This work presents an innovative strategy using biocide-loaded iron oxide nanoparticles transported within the matrix via a magnetic field to eradicate biofilms. Results show that the active delivery of the biocide to underlying cells effectively penetrates the extracellular matrix and inactivates Methicillin resistant Staphylococcus aureus (MRSA) biofilms (responsible for several difficult-to-treat infections in humans). To optimize this treatment, the loading of spherical, cubic and tetrapod-shaped nanoparticles with a model biocide, CTAB (cetyltrimethylammonium bromide) was studied. Biocide loading was determined to be dependent on the shapes' surface charge density instead of the surface area, meaning that biocide attachment is greater for nanoparticles with sharp edges (e.g. cubes and tetrapods). These results can be used to optimize treatment efficacy, and help further understanding of biofilm and nanoparticle surface zeta potentials, and the nanoparticle-biofilm interactions.


Assuntos
Antibacterianos , Biofilmes/efeitos dos fármacos , Cetrimônio , Campos Magnéticos , Nanopartículas de Magnetita/química , Staphylococcus aureus Resistente à Meticilina/fisiologia , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/crescimento & desenvolvimento , Cetrimônio/química , Cetrimônio/farmacologia
13.
Nanoscale ; 11(42): 19980-19993, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31603160

RESUMO

Despite the lysosomal "proton sponge hypothesis" being considered to be an additional factor for stimulating the cellular toxicity of nanoparticle-based drug delivery systems, a clear relationship between the massive influx of calcium ions and the proton sponge effect, both of which are associated with cancer cell apoptosis, has still not been elucidated. Cetrimonium bromide (CTAB: cationic quaternary amino group based) gold nanorods possessed a more effective electric surface charge for inducing the lysosomal proton sponge effect than anionic gold nanoparticles. In this aspect, identifying released cytoplasmic Cl-, arising from the ruptured lysosomal compartment, in the cytoplasm is critical for supporting the "proton sponge hypothesis". This study clarified that the burst release of Cl-, as a result of lysosomal swelling by CTAB gold nanorods, stimulates the transient receptor potential channels melastatin 2 (TRPM2) channels, and subsequently induces a massive Ca2+ influx, which independently increases apoptosis of cancer cells. Although the previous concept of elevated cancer apoptosis acting through the proton sponge effect is unclear, this study supports the evidence that a massive Ca2+ influx mediated in response to a burst release of Cl- significantly influenced cytotoxicity of cancer cells in tumor tissues.


Assuntos
Apoptose/efeitos dos fármacos , Ouro , Lisossomos , Nanopartículas Metálicas , Nanotubos/química , Proteínas de Neoplasias , Neoplasias Experimentais , Canais de Cátion TRPM , Animais , Linhagem Celular Tumoral , Cetrimônio/química , Cetrimônio/farmacologia , Feminino , Ouro/química , Ouro/farmacologia , Humanos , Lisossomos/genética , Lisossomos/metabolismo , Lisossomos/patologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Colloids Surf B Biointerfaces ; 183: 110421, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31401463

RESUMO

Using the electron paramagnetic resonance (EPR) of spin-labeled stearic acid and a spin label chemically attached to the membrane proteins, the interaction of miltefosine (MIL) and the ionic surfactants sodium dodecyl sulfate (SDS, anionic), cetyltrimethylammonium chloride (CTAC, cationic) and N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS, zwitterionic) with the plasma membrane of Leishmania (L.) amazonensis promastigotes was studied. The spin-label EPR data indicated that the four compounds studied have the ability to increase the molecular dynamics of membrane proteins to a large extent. Compared to the other compounds, SDS produced the smallest increases in dynamics and demonstrated the lowest antileishmanial activity and cytotoxicity to J774.A1 macrophages. The activities of the other three compounds were not different from each other, but CTAC had a stronger activity against L. amazonensis promastigotes at higher cellular concentrations (> 1 × 109 cells/mL) and was the most effective against L. amazonensis-infected macrophages. However, CTAC was also the most cytotoxic to macrophages. By measuring the IC50/CC50 values for assays of different cell concentrations, we estimated the membrane-water partition coefficient (KM/W) as well as the concentrations in the membrane (cm50) and aqueous phase (cw50) of the compounds at their IC50/CC50. Compared to the other compounds, SDS showed the lowest value of KM/W and the highest value of cm50. In all experiments in this study, the data for the zwitterionic molecules HPS and MIL were not significantly different.


Assuntos
Antiprotozoários/farmacologia , Cetrimônio/farmacologia , Citotoxinas/farmacologia , Leishmania braziliensis/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Dodecilsulfato de Sódio/farmacologia , Tensoativos/farmacologia , Antiprotozoários/química , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Cetrimônio/química , Citotoxinas/química , Espectroscopia de Ressonância de Spin Eletrônica , Humanos , Concentração Inibidora 50 , Leishmania braziliensis/crescimento & desenvolvimento , Leishmania braziliensis/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Simulação de Dinâmica Molecular , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia , Compostos de Amônio Quaternário/química , Dodecilsulfato de Sódio/química , Marcadores de Spin , Ácidos Esteáricos/química , Tensoativos/química
15.
Anticancer Res ; 39(7): 3621-3631, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262888

RESUMO

BACKGROUND/AIM: Cetrimonium bromide (CTAB), a quaternary ammonium surfactant, is an antiseptic agent against bacteria and fungi. However, the mechanisms by which its pharmacological actions affect epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells, such as adenocarcinoma in SK-HEP-1 cells, have not been investigated. We, thereby, investigated whether CTAB inhibits cellular mobility and invasiveness of human hepatic adenocarcinoma in SK-HEP-1 cells. MATERIALS AND METHODS: SK-HEP-1 cells were treated with CTAB, and subsequent migration and invasion were measured by wound healing and transwell assays. Protein expression was detected by immunoblotting analysis. RESULTS: Our data revealed that treatment of SK-HEP-1 cells with CTAB altered their mesenchymal spindle-like morphology. CTAB exerted inhibitory effects on the migration and invasion of SK-HEP-1 cells dose-dependently, and reduced protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9, snail, slug, twist, vimentin, fibronectin, N-cadherin, Smad2, Smad3, Smad4, phosphoinositide-3-kinase (PI3K), p-PI3K, Akt, p-Akt, ß-catenin, mammalian target of rapamycin (mTOR), p-mTOR, p-p70S6K, p-extracellular signal-regulated kinases (ERK)1/2, p-p38 mitogen-activated protein kinase (MAPK) and p-c-Jun N-terminal kinase (JNK), but increased protein levels of tissue inhibitor matrix metalloproteinase-1 (TIMP-1), TIMP-2, claudin-1 and p-GSK3ß. Based on these observations, we suggest that CTAB not only inhibits the canonical transforming growth factor-ß (TGF-ß) signaling pathway though reducing SMADs (an acronym from the fusion of Caenorhabditis elegans Sma genes and the Drosophila Mad, Mothers against decapentaplegic proteins), but also restrains the non-canonical TGF-ß signaling including MAPK pathways like ERK1/2, p38 MAPK, JNK and PI3K. CONCLUSION: CTAB is involved in the suppression of TGF-ß-mediated mesenchymal phenotype and could be a potent medical agent for use in controlling the migration and invasion of hepatic adenocarcinoma.


Assuntos
Adenocarcinoma/metabolismo , Antineoplásicos/farmacologia , Cetrimônio/farmacologia , Neoplasias Hepáticas/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adenocarcinoma/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacos
16.
J. appl. oral sci ; 27: e20180157, 2019. tab, graf
Artigo em Inglês | LILACS, BBO | ID: biblio-975884

RESUMO

Abstract Objectives The aim of this study was to evaluate the influence of surfactants 0.2% or 0.1% cetrimide (Cet) or 0.008% benzalkonium chloride (BAK) on 2.5% calcium hypochlorite (Ca(OCl)2), and compare to sodium hypochlorite (NaOCl), regarding the properties of pH, free chlorine content, surface tension, contact angle, pulp dissolution and antimicrobial activity. Material and Methods The pH and free chlorine content were evaluated by digital pHmeter and by titration, respectively. Surface tension was measured by the platinum ring technique with a Du Noüy tensiometer. The solution's contact angle in human dentin surfaces was checked by Drop Shape Analyzer software. Bovine pulps were used for pulp dissolution analysis and the dissolving capacity was expressed by percent weight loss. Antimicrobial activity over Enterococcus faecalis was evaluated by the agar diffusion method. Results Surfactants addition to Ca(OCl)2 and NaOCl did not alter the pH, free chlorine content and pulp dissolution properties. Ca(OCl)2 had the highest surface tension among all tested solutions. When surfactants were added to Ca(OCl)2 and NaOCl, there was a significant reduction of surface tension and contact angle values. The addition of 0.2% or 0.1% Cet enhanced antimicrobial activity of both Ca(OCl)2 and NaOCl. Conclusion Surfactant addition to 2.5% Ca(OCl)2 has shown acceptable outcomes for pH, free chlorine content, surface tension, contact angle, pulp dissolution and antimicrobial activity. Furthermore, the addition of 0.2% Cet showed better results for all tested properties.


Assuntos
Humanos , Animais , Bovinos , Irrigantes do Canal Radicular/química , Hipoclorito de Sódio/química , Tensoativos/química , Compostos de Benzalcônio/química , Compostos de Cálcio/química , Cetrimônio/química , Valores de Referência , Hipoclorito de Sódio/farmacologia , Tensoativos/farmacologia , Propriedades de Superfície , Compostos de Benzalcônio/farmacologia , Teste de Materiais , Cloro/análise , Reprodutibilidade dos Testes , Análise de Variância , Enterococcus faecalis/efeitos dos fármacos , Compostos de Cálcio/farmacologia , Estatísticas não Paramétricas , Polpa Dentária/efeitos dos fármacos , Dentina/efeitos dos fármacos , Cetrimônio/farmacologia , Concentração de Íons de Hidrogênio
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