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1.
Nature ; 579(7798): 260-264, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32132711

RESUMEN

The production of pore-forming toxins that disrupt the plasma membrane of host cells is a common virulence strategy for bacterial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA)1-3. It is unclear, however, whether host species possess innate immune mechanisms that can neutralize pore-forming toxins during infection. We previously showed that the autophagy protein ATG16L1 is necessary for protection against MRSA strains encoding α-toxin4-a pore-forming toxin that binds the metalloprotease ADAM10 on the surface of a broad range of target cells and tissues2,5,6. Autophagy typically involves the targeting of cytosolic material to the lysosome for degradation. Here we demonstrate that ATG16L1 and other ATG proteins mediate protection against α-toxin through the release of ADAM10 on exosomes-extracellular vesicles of endosomal origin. Bacterial DNA and CpG DNA induce the secretion of ADAM10-bearing exosomes from human cells as well as in mice. Transferred exosomes protect host cells in vitro by serving as scavengers that can bind multiple toxins, and improve the survival of mice infected with MRSA in vivo. These findings indicate that ATG proteins mediate a previously unknown form of defence in response to infection, facilitating the release of exosomes that serve as decoys for bacterially produced toxins.


Asunto(s)
Proteínas Relacionadas con la Autofagia/metabolismo , Toxinas Bacterianas/metabolismo , Exosomas/metabolismo , Células A549 , Proteína ADAM10/metabolismo , Animales , Toxinas Bacterianas/farmacología , Supervivencia Celular/efectos de los fármacos , ADN Bacteriano/farmacología , Exosomas/efectos de los fármacos , Exosomas/ultraestructura , Femenino , Células HEK293 , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Staphylococcus aureus Resistente a Meticilina/fisiología , Ratones , Ratones Endogámicos C57BL , Infecciones Estafilocócicas/mortalidad
2.
Chem Biol Interact ; 320: 109022, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32112862

RESUMEN

Epithelial mesenchymal transformation plays a crucial role in the metastasis of bladder cancer, which makes bladder cancer difficult to cure. Bladder cancer is the most common malignancy of the urinary system, and distant metastasis is the leading cause of death. Therefore, finding a bioactive drug that can specifically inhibit epithelial mesenchymal transformation may be a new direction for bladder cancer treatment in the future. Thymoquinone (TQ), the major active compound isolated from black seed oil (Nigella sativa), has been reported to exhibit anti-inflammatory and anticancer abilities. TQ can exhibit its antitumor effect by inhibiting the proliferation and metastasis of cancer cells. However, the underlying mechanism of TQ as a tumor inhibitor in bladder cancer remains poorly understood. First, in this research, we demonstrate that TQ can reverse EMT by upregulating epithelial markers, such as E-cadherin, and downregulating mesenchymal markers, such as N-cadherin and vimentin. Furthermore, we demonstrate that TQ can suppress the activation of the Wnt/ß-catenin signaling pathway and inhibit the expression of ß-catenin target genes, such as MYC, Axin-2, MMP7, CyclinD1 and MET, which play crucial roles in EMT and cancer progression. Additionally, we demonstrate that TQ can inhibit the growth of xenografts and restrict the formation of tumor metastatic foci in the lung. Taken together, our findings confirm the antimetastatic effect of TQ in bladder cancer cells for the first time and also provide new evidence for the development of TQ as a novel treatment for metastatic bladder cancer.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Benzoquinonas/farmacología , Supervivencia Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Benzoquinonas/química , Línea Celular Tumoral , Ensayos de Migración Celular , Movimiento Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Estructura Molecular , Proteínas Wnt/genética , beta Catenina/genética
3.
Chem Biol Interact ; 320: 109029, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32119866

RESUMEN

Geraniol (GOH), like other plant-derived natural bioactive compounds, has been found to possess antiproliferative properties that are essential to cope with malignant tumors. However, the mechanisms of molecular action of GOH are not fully elucidated. The aim of this study was to evaluate the effect of GOH on some oxidative parameters in human tumor cell lines (HepG2 and A549). Cytotoxicity evaluated in cell lines by the MTT assay, genotoxicity by the comet assay, and lipid peroxidation by the TBARS. The activities of antioxidant the enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST), were also analyzed. Additionally, intracellular reactive oxygen species (ROS), nitric oxide, and lactate production were determined in HepG2 cells. Both tumor cell lines showed a clear concentration-dependent response to GOH in several of the parameters evaluated. Lipids turned out to be more sensitive than DNA to oxidative damage induced by GOH. TBARS levels increased with respect to control (p < 0.05) by 33% and 122% in HepG2 and A549 cells, respectively treated with 200 µM GOH. However, GOH caused a statistically significant decrease in SOD and CAT activities in HepG2 cells only. GST was not affected in any cell lines. GOH induced the production of ROS but not nitric oxide in HepG2, which shows that ROS were mainly responsible for oxidative damage. Lactate release increased statistically significantly compared to control (p < 0.001), by 41% and 86% at 200 and 800 µM GOH respectively, showing that this monoterpene also affected the glycolytic pathway in HepG2 cells. These results suggest that oxidative stress could mediate the anti-proliferative effects of GOH in HepG2 and A549 cells.


Asunto(s)
/farmacología , Proliferación Celular , Estrés Oxidativo/efectos de los fármacos , Células A549 , /química , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Hep G2 , Humanos , Estructura Molecular
4.
Chem Biol Interact ; 321: 109025, 2020 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-32135139

RESUMEN

Epigenetic regulation is one of the driving forces in the process of carcinogenesis. Corosolic acid (CA); triterpenoid abundantly found in Lagerstroemia speciosa L. is known to modulate various cellular process including cellular oxidative stress and signaling kinases in various diseases, including skin cancer. Genetic mutations in early stages of skin cancer are well-documented, the epigenetic alterations remain elusive. In the present study, we identified the transcriptomic gene expression changes with RNAseq and genome-wide DNA CpG methylation changes with DNA methylseq to profile the early stage transcriptomic and epigenomic changes using tumor promoter TPA-mediated mouse epidermal epithelial JB6 P+ cells. JB6 P+ cells were treated with TPA and Corosolic acid by 7.5uM optimized by MTS assay. Differentiated expressed genes (DEGs) and Differentially methylated genes (DMRs) were analyzed by R software. Ingenuity Pathway Analysis (IPA) was employed to understand the differential regulation of specific pathways. Novel TPA induced differentially overexpressed genes like tumor promoter Prl2c2, small prolin rich protein (Sprr2h) was reported which was downregulated by corosolic acid treatment. Several cancer related pathways were identified by Ingenuity Pathways Analysis (IPA) including p53, Erk, TGF beta signaling pathways. Moreover, differentially methylated regions (DMRs) in genes like Dusp22 (Dual specificity protein phosphatase 22), Rassf (tumor suppressor gene family, Ras association domain family) in JB6 P+ cells were uncovered which are altered by TPA and are reversed by CA treatment. Interestingly, genes like CDK1 (Cyclin-dependent kinases 1) and RASSF2 (Ras association domain family member 2) observed to be differentially methylated and expressed which was further modulated by corosolic acid treatment, validated by qPCR. Given study indicated gene expression changes to DNA CpG methylation epigenomic changes modulated various molecular pathways in TPA-induced JB6 cells and revealed that CA can potentially reverse these changes which deciphering novel molecular targets for future prevention of early stages of skin cancer studies in human.


Asunto(s)
Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/metabolismo , Metilación de ADN/efectos de los fármacos , Células Epidérmicas/efectos de los fármacos , Células Epidérmicas/metabolismo , Triterpenos/farmacología , Animales , Carcinógenos/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Transformación Celular Neoplásica/genética , Islas de CpG/efectos de los fármacos , Células Epidérmicas/patología , Epigénesis Genética/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones , Fitoquímicos/farmacología , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/metabolismo , Acetato de Tetradecanoilforbol/toxicidad , Transcriptoma/efectos de los fármacos
5.
Asian Pac J Cancer Prev ; 21(3): 837-843, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-32212815

RESUMEN

OBJECTIVE: ß-glucan, glucopyranosyl polymers of fungi cell wall, represent an immune stimulating effects with potential anti-cancer activity. Mesenchymal stem cells (MSC) have immunomodulating properties in cancer microenvironment. The aim of this study was to investigate the anti-cancer effect of Candida albicans (C. albicans) beta-glucan on MSCs supernatant for apoptosis assay of lung cancer cells in vitro. METHODS: Beta-glucan was extracted from cell wall of C.albicans. MSC isolated from adipose tissue of patients and confirmed using specific surface markers expression which examined by flow cytometry. MSCs treated with various concentrations of ß-glucans for 48 hours. Cytotoxic effect of ß-glucans was evaluated using MTT assay. MSC and lung cancer line cocultured and treated with ß-glucans and apoptosis assay was done by flow cytometry. RESULTS: Cytotoxicity findings showed a significant decrease in MSC viability during 48h, however it was dose-dependent (P<0.05). According to the obtained findings, supernatant of mesenchymal stem cells treated with ß-glucans increased cancer cells apoptosis (P<0.05). CONCLUSION: Beta glucan may highlight a potential and novel promising candidate in future strategies to cause apoptosis of cancer cells and consider as therapeutic  agent against tumor growth as well. Definitely, more in vitro and in vivo studies are required to understand its functions.


Asunto(s)
Candida albicans/química , Neoplasias Pulmonares/patología , Células Madre Mesenquimatosas/efectos de los fármacos , beta-Glucanos/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Humanos , Células Madre Mesenquimatosas/citología
6.
Braz Oral Res ; 34: e013, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32074213

RESUMEN

This study evaluated the effect of a cyclopentenone-type PG, 15-Deoxy-Δ12,14-PG J2 (15d-PGJ2), and lectin (ScLL) on the viability of human gingival fibroblasts (HGFs), and on IL-6 and TGFß-1 release by these fibroblasts, stimulated with lipopolysaccharide (LPS). HGFs were stimulated with LPS 10 µg/ml and treated with 15d-PGJ2 1 and 2 µg/ml, and ScLL 2 and 5 µg/ml, for 1 and 3h, and then evaluated for viability by MTT assay. Supernatant was collected to detect IL-6 and TGFß-1 release, by ELISA. Positive control was cells kept in Dulbecco's Modified Eagle's Medium, and negative control was those kept in LPS. Data were analyzed by ANOVA and Dunnett's test (α = 0.05). No significant difference was found in viability among experimental groups at 1h (p > 0.05). Percentage of ScLL 5 µg/ml viable cells was similar to that of positive control at evaluated periods (p > 0.05), whereas the other groups had lower levels than the positive control (p < 0.05). IL-6 release was statistically higher for ScLL 5 µg/ml and 15d-PGJ2 2 µg/ml at 1h, compared with the other treated groups and positive control (p < 0.05). No significant differences were found among the groups at 3h (p > 0.05), except for ScLL 2 µg/ml and 15d-PGJ2 1 µg/ml, which showed lower IL-6 release compared with that of negative control (p < 0.05). No significant difference was found among the groups for TGFß-1 release (p > 0.05). Results indicated that ScLL 5 µg/ml did not interfere in viability, and ScLL 2 µg/ml and 15d-PGJ2 1 µg/ml demonstrated reduced IL-6 release. Tested substances had no effect on TGFß-1 release.


Asunto(s)
Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Lectinas de Plantas/farmacología , Prostaglandina D2/análogos & derivados , Factor de Crecimiento Transformador beta1/metabolismo , Análisis de Varianza , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Encía/citología , Humanos , Prostaglandina D2/farmacología , Valores de Referencia , Estadísticas no Paramétricas , Factores de Tiempo , Factor de Crecimiento Transformador beta1/efectos de los fármacos
7.
Chem Biol Interact ; 317: 108965, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-32001260

RESUMEN

Endocrine therapies (e.g. tamoxifen and aromatase inhibitors) targeting estrogen action are effective in decreasing mortality of breast cancer. However, their efficacy is limited by intrinsic and acquired resistance. Our previous study demonstrated that overexpression of a histone methyltransferase NSD2 drives tamoxifen resistance in breast cancer cells and that NSD2 is a potential biomarker of tamoxifen resistant breast cancer. Here, we found that DZNep, an indirect inhibitor of histone methyltransferases, potently induces the degradation of NSD2 protein and inhibits the expression of NSD2 target genes (HK2, G6PD, GLUT1 and TIGAR) involved in the pentose phosphate pathway (PPP). DZNep treatment of tamoxifen-resistant breast cancer cells and xenograft tumors also strongly inhibits tumor growth and the cancer cell survival through decreasing cell production of NADPH and glutathione (GSH) and invoking elevated ROS to cause apoptosis. These findings suggest that DZNep-like agents can be developed to target NSD2 histone methyltransferase for effective treatment of tamoxifen-resistant breast cancer.


Asunto(s)
Adenosina/análogos & derivados , N-Metiltransferasa de Histona-Lisina/metabolismo , Metiltransferasas/antagonistas & inhibidores , Proteínas Represoras/metabolismo , S-Adenosilhomocisteína/metabolismo , Adenosina/farmacología , Antígenos Ly , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , N-Metiltransferasa de Histona-Lisina/genética , Homeostasis , Humanos , Oxidación-Reducción , Proteolisis/efectos de los fármacos , Especies Reactivas de Oxígeno , Proteínas Represoras/genética , Tamoxifeno , Activador de Plasminógeno de Tipo Uroquinasa
8.
Cell Physiol Biochem ; 54(2): 161-179, 2020 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-32045141

RESUMEN

BACKGROUND/AIMS: We performed co-culture experiments between human RPE cells (ARPE-19) and human umbilical vascular endothelial cells (HUVEC) in order to evaluate how anti-VEGF drugs could affect NO release, mitochondrial function, the oxidative status, proliferation and migration of RPE cells through modulation of their cross talk with vascular endothelial cells. METHODS: The co-culture HUVEC/RPE, was exposed to Ranibizumab/Aflibercept in the absence/presence of the NO synthase (NOS) inhibitor, the phosphatidylinositol 3'-kinase (PI3K), the extracellular-signal-regulated kinases 1/2 (ERK1/2) and the p38 mitogen-activated protein kinase (p38 MAPK) blockers. Specific kits were used for cell viability, mitochondrial membrane potential, NO, ROS and GSH production. Western blot was performed for apoptosis markers, NOS isoforms, and others kinases detection. Cell migration was analyzed by scratch assay, whereas cell proliferation and cell cycle through xCELLigence and flow cytometry. RESULTS: In RPE cells co-cultured with HUVEC in physiological conditions, Aflibercept/Ranibizumab increased NO release in a dose and time-dependent way. Opposite results were obtained in peroxidative conditions. Both anti-VEGF agents were able to prevent the fall of cell viability and mitochondrial membrane potential, an effect which was reduced by various inhibitors, and increased cell migration. Aflibercept/Ranibizumab counteracted the changes of apoptosis markers, NOS expression/activation, PI3K and ERK1/2 activation caused by peroxidation. These results were confirmed by cell cycle analysis. CONCLUSION: This study has shown new mechanisms at the basis of protective effects elicited by Aflibercept/Ranibizumab in RPE cells. HUVEC stimulated with Aflibercept/Ranibizumab, could release some paracrine factors that can modulate the RPE cells response in both physiologic and peroxidative conditions.


Asunto(s)
Comunicación Celular/efectos de los fármacos , Ranibizumab/farmacología , Proteínas Recombinantes de Fusión/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Técnicas de Cocultivo , Glutatión/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular , Epitelio Pigmentado de la Retina/citología , Epitelio Pigmentado de la Retina/metabolismo
9.
Toxicol Lett ; 325: 14-24, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-32062016

RESUMEN

Because of their antimicrobial properties, silver nanoparticles are increasingly incorporated in food-related and hygiene products, which thereby could lead to their ingestion. Although their cytotoxicity mediated by oxidative stress has been largely studied, their effects on inflammation remain controversial. Moreover, the involvement of silver ions (originating from Ag0 oxidation) in their mode of action is still unclear. In this context, the present study aims at assessing the impact of silver nanoparticles on the secretion of the pro-inflammatory chemokine interleukin-8 by Caco-2 cells forming an in vitro model of the intestinal mucosal barrier. Silver nanoparticles induced a vectorized secretion of interleukin-8 towards the apical compartment, which is found in the medium 21 h after the incubation. This secretion seems mediated by Nrf2 signalling pathway that orchestrates cellular defense against oxidative stress. The soluble silver fraction of silver nanoparticles suspensions led to a similar amount of secreted interleukin-8 than silver nanoparticles, suggesting an involvement of silver ions in this interleukin-8 secretion.


Asunto(s)
Interleucina-8/metabolismo , Nanopartículas del Metal/toxicidad , Plata/toxicidad , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Colon/efectos de los fármacos , Enteritis/inducido químicamente , Enteritis/patología , Expresión Génica/efectos de los fármacos , Humanos , Inflamación/inducido químicamente , Inflamación/patología , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula
10.
Biochemistry (Mosc) ; 85(2): 205-212, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32093596

RESUMEN

Thymoquinone (TQ) exhibits a wide spectrum of biological activities. Most studies on the neurotoxic action of TQ have been carried out in cancer cell lines. Here, we studied the toxic effect of TQ in primary neuronal cultures in vitro. Incubation with 0.04-0.05 mM TQ for 24 h induced the death of cultured cerebellar granule neurons (CGNs) in a dose-dependent manner. Neuronal death was preceded by an increase in the reactive oxygen species (ROS) generation, as demonstrated using CellROX Green and MitoSOX Red. Confocal and electron microscopy showed that incubation with 0.05 mM TQ for 5 h induced changes in the intracellular localization of mitochondria and mitochondria hypertrophy and cell swelling. The antioxidant N-acetyl-L-cysteine (2 mM) protected CGNs from the toxic action of TQ. Taken together, these facts suggest that TQ is toxic for normal neurons, while ROS-induced changes in the mitochondria can be one of the major causes of the TQ-induced neuronal damage and death.


Asunto(s)
Benzoquinonas/toxicidad , Gránulos Citoplasmáticos/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Neuronas/efectos de los fármacos , Animales , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Gránulos Citoplasmáticos/metabolismo , Relación Dosis-Respuesta a Droga , Mitocondrias/metabolismo , Neuronas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/análisis , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad
11.
Life Sci ; 248: 117456, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32097666

RESUMEN

AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.


Asunto(s)
Antiinflamatorios/farmacología , Berberina/farmacología , Gastritis Atrófica/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Factores Reguladores del Interferón/genética , Interferón gamma/genética , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quimiocina CXCL1/antagonistas & inhibidores , Quimiocina CXCL1/genética , Quimiocina CXCL1/inmunología , Quimiocina CXCL9/antagonistas & inhibidores , Quimiocina CXCL9/genética , Quimiocina CXCL9/inmunología , Enfermedad Crónica , Modelos Animales de Enfermedad , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Células Epiteliales/microbiología , Gastritis Atrófica/genética , Gastritis Atrófica/inmunología , Gastritis Atrófica/microbiología , Regulación de la Expresión Génica , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/crecimiento & desarrollo , Helicobacter pylori/patogenicidad , Humanos , Factores Reguladores del Interferón/antagonistas & inhibidores , Factores Reguladores del Interferón/inmunología , Interferón gamma/antagonistas & inhibidores , Interferón gamma/inmunología , Interleucina-17/agonistas , Interleucina-17/genética , Interleucina-17/inmunología , Masculino , Proteínas NLR/antagonistas & inhibidores , Proteínas NLR/genética , Proteínas NLR/inmunología , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Uridina Fosforilasa/antagonistas & inhibidores , Uridina Fosforilasa/genética , Uridina Fosforilasa/inmunología
12.
J Photochem Photobiol B ; 204: 111808, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32006892

RESUMEN

Photodynamic therapy (PDT) is effective in the treatment of different types of cancer, such as basal cell carcinoma and other superficial cancers. However, improvements in photosensitizer delivery are still needed, and the use of PDT against more deeply located tumors has been the subject of many studies. Thus, the goal of this study was to evaluate the efficacy of a nanoemulsion containing aluminium-phthalocyanine (AlPc-NE) as a mediator of photodynamic therapy (PDT-AlPc-NE) against grafted 4T1 breast adenocarcinoma tumors in mice (BALB/c). Short after the appearance of the tumor, the animals were divided into groups (n = 5) as follows: untreated; only AlPc-NE and treated with PDT-AlPc-NE. The tumor volume was measured with a digital calliper at specific times. The presence of metastasis in the lungs was evaluated by microtomography and histopathological analyses. The results show that the application of PDT-AlPc-NE eradicated the transplanted tumors in all the treated animals, while the animals from control groups presented a robust increase in the tumor volume. Still more significantly, microtomography showed the animals submitted the PDT-AlPc-NE to be free of detectable metastasis in the lungs. The histological analysis of the lungs further confirmed the results verified by the microtomography. Therefore, this study suggests that PDT-AlPc-NE is effective in the elimination of experimentally grafted breast tumors in mice and also in preventing the formation of metastasis in the lungs.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Aluminio/química , Neoplasias de la Mama/tratamiento farmacológico , Indoles/química , Neoplasias Pulmonares/tratamiento farmacológico , Nanoestructuras/química , Fármacos Fotosensibilizantes/uso terapéutico , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Animales , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Nanoestructuras/uso terapéutico , Nanoestructuras/toxicidad , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Trasplante Homólogo , Microtomografía por Rayos X
13.
J Photochem Photobiol B ; 204: 111767, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32006893

RESUMEN

Colon carcinoma is a recurring type of cancer that affects the intestine epithelial with a poor survival rate. It was already proven the anticancer property of hesperidin in various cancers but the bioavailability hesperidin is poor, which hinders the hesperidin usage. In this investigation we synthesized hesperidin loaded Zn2+@ SA/PCT nanocomposites and assessed its anticancer potential against colon cancer (HCT116) cells. Hesperidin loaded Zn2+@ SA/PCT nanocomposites were characterized using Fourier transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM) and transmission electron microscope (TEM) analysis. The drug releasing capacity and cytotoxic property was assessed via drug releasing assay, MTT assay with HCT116 cells. The anticancer potency of hesperidin nanocomposites were evaluated with TUNEL, DAPI staining, reactive oxygen species (ROS) generation assay and it is confirmed with flow cytometry analysis of MMP disruption in colon cancer (HCT116) cell line. Further the immunoblotting analysis of cysteine proteases Caspases 3, 9, PARP, proapoptotic protein Bax and antiapoptotic protein Bcl2 were performed. The results of FTIR, XRD and electroscopic analyses confirmed the synthesized hesperidin nanocomposites accomplish the properties of potent nanodrug and the MTT assay authentically confirmed that the synthesized hesperidin nanocomposite inhibited the HCT116 cell growth, and the results of fluorescent staining proved that the hesperidin nanocomposite induced the apoptotic mediated cell necrosis via promoting the expression of apoptotic proteins thereby induced the apoptosis in colon cancer (HCT116) cells. Hence, it was concluded that the, hesperidin loaded nanocomposites persuasively inhibited proliferation of colon carcinoma cell and induced apoptosis in in vitro condition.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Hesperidina/química , Nanocompuestos/química , Alginatos/química , Antineoplásicos Fitogénicos/química , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Composición de Medicamentos , Liberación de Fármacos , Células HCT116 , Hesperidina/farmacología , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Pectinas/química , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Zinc/química
14.
J Phys Chem Lett ; 11(4): 1357-1363, 2020 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-32017568

RESUMEN

Large doses of anticancer drugs entering cancer cell nuclei are found to be effective at killing cancer cells and increasing chemotherapeutic effectiveness. Here we report red-emissive carbon quantum dots, which can enter into the nuclei of not only cancer cells but also cancer stem cells. After doxorubicin was loaded at the concentration of 30 µg/mL on the surfaces of carbon quantum dots, the average cell viability of HeLa cells was decreased to only 21%, while it was decreased to 50% for free doxorubicin. The doxorubicin-loaded carbon quantum dots also exhibited a good therapeutic effect by eliminating cancer stem cells. This work provides a potential strategy for developing carbon quantum-dot-based anticancer drug carriers for effective eradication of cancers.


Asunto(s)
Carbono/química , Núcleo Celular/metabolismo , Doxorrubicina/metabolismo , Portadores de Fármacos/química , Puntos Cuánticos/química , Animales , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Células HeLa , Humanos , Ratones , Ratones Desnudos , Microscopía Confocal , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Trasplante Heterólogo
15.
J Photochem Photobiol B ; 204: 111799, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32018156

RESUMEN

CdSe/CdS core shelled quantum dots (QDs) were prepared by colloidal synthesis using a binary ligand system and a non-coordinating, reusable solvent n-octadecane (nOD). Both the synthesis of CdSe and CdSe/CdS core shelled quantum dots were achieved by hot injection technique at much lower temperatures than reported earlier. The use of binary ligand facilitated enough nucleation and growth. Red shift in absorption spectra, an enhanced crystallite and particle size is evidenced by XRD and TEM respectively, confirming the formation of core shell structure of CdSe/CdS. The synthesized core shells exhibited high fluorescence intensity, long term stability and good mono dispersion, making it a potential material for bio-imaging and sensing. Core shell QDs were modified with mercapto propionic acid (MPA) to impart aqueous solubility. Studies on cytotoxicity of shelled QDs reveal good bio compatibility with a very minimum toxicity of IC50 = 20 µg/L. These QDs were used for sensing E. coli. Ordinary glass slide, modified using plasma etching is surface modified through APTES aiding conjugation of antibodies. Anti- E. coli polyclonal antibody on glass matrix (slide) and antibody conjugated QDs were used for detection of E. coli in a typical sandwich model. The excellent optical transparency of glass and high emission of QDs lead to detection of E.coli with a limit of detection of 50 CFU/mL.


Asunto(s)
Escherichia coli/efectos de los fármacos , Vidrio/química , Puntos Cuánticos/química , Animales , Compuestos de Cadmio/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ratones , Microscopía Fluorescente , Puntos Cuánticos/toxicidad , Compuestos de Selenio/química , Sulfuros/química , Propiedades de Superficie
16.
J Photochem Photobiol B ; 204: 111806, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32044619

RESUMEN

The cotton fabrics are a cosmopolitan in usage due to their extraordinary features. The clothes are a very good medium for the growth of pathogenic microorganisms. The nanoparticles have diverse benefits in the biomedical field like drug carrier and as antimicrobials. The current investigation was aimed to synthesize the metallic silver nanoparticles (AgNPs) from the aqueous extract of Curcuma longa leaf and evaluating their antimicrobial and wound healing potential of AgNPs coated cotton fabric. The synthesized AgNPs were characterized by HR-TEM and FT-IR examinations. The formulated AgNPs were coated with cotton fabrics to test their efficiency against the pathogenic microorganisms. The existence of AgNPs in the cotton fabrics was confirmed via the SEM along with EDX analysis. The antimicrobial potential of fabricated AgNPs and its coated cotton fabrics was inspected against the human pathogenic strains. The wound healing efficacy was examined in the L929 cells. The HR-TEM analysis proved the existence of spherical shaped AgNPs. In the antimicrobial activity, the CL-AgNPs loaded cotton fabric was exhibited an appreciable decrease in the growth of pathogenic microorganisms. The crude extract, as well as formulated AgNPs, also exhibited the noticeable antimicrobial potency against the S.aureus, P.aeruginosa, S.pyogenes, and C.albicans. The AgNPs loaded cotton fabrics was displayed the potent wound healing activity in the fibroblast (L929) cells. Consequently, it was concluded that the formulated AgNPs from C.longa coated cotton fabrics may be utilized for the variety of applications in hospital patients and even medical workers to prevent the microbial infection.


Asunto(s)
Antiinfecciosos/química , Fibra de Algodón/análisis , Curcuma/química , Nanopartículas del Metal/química , Plata/química , Animales , Antiinfecciosos/farmacología , Candida albicans/efectos de los fármacos , Línea Celular , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Curcuma/metabolismo , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Tecnología Química Verde , Nanopartículas del Metal/toxicidad , Ratones , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/química , Hojas de la Planta/química , Hojas de la Planta/metabolismo
17.
J Photochem Photobiol B ; 204: 111587, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32062387

RESUMEN

Although the photothermal therapy (PTT) has achieved tremendous progress in the recent times, still it has to improve an extensive way to achieve the efficient targeted photothermal removal of the tumor cells. Owing to this requirement, we demonstrated a novel class of reduced graphene oxide based photothermal therapeutic agent for the ablation of lung cancer cells (A549). A single step bio facile fabrication of graphene nanosheets using Memecylon edule leaf extract intermediated reduction of Graphene Oxide (GO). This process does not include the utilization of any toxic or harmful reducing agents. The relative results of different characterizations of graphene oxide and Memecylon edule leaf extract RGO delivers a potential representation by excluding the groups containing oxygen from GO and consecutive stabilization of the developed RGO. The reduced GO functionalization with the oxidized polyphenols results in their stability by avoiding the aggregation. The poly phenol anchored Reduced Graphene Oxide (RGO) exhibited exceptional near-infrared (NIR) irradiation of the lung cancer cells directed in vitro to deliver cytotoxicity. In an area of restricted success in the treatment of cancer, the results of our translation can provide a path for designing targeted PTT agents and also responds to stimulus environment for the safe ablation of the devastating disease.


Asunto(s)
Grafito/química , Rayos Infrarrojos , Nanoestructuras/química , Polifenoles/química , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Perros , Tecnología Química Verde , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Células de Riñón Canino Madin Darby , Magnoliopsida/química , Magnoliopsida/metabolismo , Nanoestructuras/uso terapéutico , Nanoestructuras/toxicidad , Fototerapia/métodos , Extractos Vegetales/química , Hojas de la Planta/química , Hojas de la Planta/metabolismo
18.
Nat Commun ; 11(1): 74, 2020 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-31900393

RESUMEN

Despite the promising clinical efficacy of the second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib in patients with ALK-rearranged lung cancer, some tumor cells survive and eventually relapse, which may be an obstacle to achieving a cure. Limited information is currently available on the mechanisms underlying the initial survival of tumor cells against alectinib. Using patient-derived cell line models, we herein demonstrate that cancer cells survive a treatment with alectinib by activating Yes-associated protein 1 (YAP1), which mediates the expression of the anti-apoptosis factors Mcl-1 and Bcl-xL, and combinatorial inhibition against both YAP1 and ALK provides a longer tumor remission in ALK-rearranged xenografts when compared with alectinib monotherapy. These results suggest that the inhibition of YAP1 is a candidate for combinatorial therapy with ALK inhibitors to achieve complete remission in patients with ALK-rearranged lung cancer.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Quinasa de Linfoma Anaplásico/genética , Apoptosis/efectos de los fármacos , Carbazoles/administración & dosificación , Reordenamiento Génico/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Piperidinas/administración & dosificación , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Quinasa de Linfoma Anaplásico/metabolismo , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/fisiopatología , Masculino , Ratones , Ratones Endogámicos BALB C , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/fisiopatología , Inhibidores de Proteínas Quinasas/administración & dosificación , Factores de Transcripción/genética
19.
J Basic Microbiol ; 60(3): 207-215, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31960983

RESUMEN

The treatment of Helicobacter pylori usually fails due to their ability to form biofilms and resistance to antibiotics. This might potentially lead to gastric carcinoma and mucosa-associated lymphoid tissue lymphoma. In the present study, we elucidate the potential role of N-acylhomoserine lactonase stabilized silver nanoparticles (AiiA-AgNPs) in treating biofilms produced by H. pylori. AiiA-AgNPs inhibited quorum sensing (QS) by degradation of QS molecules, thereby reducing biofilm formation, urease production, and altering cell surface hydrophobicity of H. pylori. AiiA-AgNPs showed no cytotoxic effects on RAW 264.7 macrophages at the effective concentration (1-5 µM) of antibiofilm activity. In addition, AiiA-AgNP in high concentration (80-100 µM) exhibited cytotoxicity against HCT-15 carcinoma cells, depicting its therapeutic role in treating cancer.


Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Hidrolasas de Éster Carboxílico/farmacología , Helicobacter pylori/efectos de los fármacos , Percepción de Quorum/efectos de los fármacos , Plata/farmacología , Animales , Antibacterianos/química , Antineoplásicos/química , Antineoplásicos/farmacología , Biopelículas/crecimiento & desarrollo , Hidrolasas de Éster Carboxílico/química , Línea Celular Tumoral , Membrana Celular/química , Membrana Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Helicobacter pylori/metabolismo , Humanos , Interacciones Hidrofóbicas e Hidrofílicas/efectos de los fármacos , Nanopartículas del Metal/química , Ratones , Células RAW 264.7 , Plata/química , Ureasa/metabolismo
20.
Anticancer Res ; 40(1): 53-66, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892552

RESUMEN

BACKGROUND/AIM: Medulloblastoma (MB) accounts for ~20% of pediatric malignant central nervous system tumors. Treatment strategies, including surgery, radiation therapy and/or chemotherapy, are effective, but recurrence and metastasis frequently occur. Therefore, novel therapies are required. Herein, the effects of fibroblast growth factor receptor (FGFR) and phosphoinositide 3-kinase (PI3K) inhibitors on MB cells lines were evaluated. MATERIALS AND METHODS: MB cell lines (UW228-3, DAOY, Med8a, D425, D283) were tested for sensitivity to FGFR (AZD4547) and PI3K (BEZ235 and BYL719) inhibitors by viability, cytotoxicity, apoptosis, and proliferation assays. RESULTS: Single treatments with FGFR and PI3K inhibitors decreased viability and proliferation in a dose-dependent pattern in most cell lines. Combinination of the two type of drugs, increased sensitivity, especially of the most resistant cell line UW228-3. CONCLUSION: Combination treatments with FGFR and PI3K inhibitors were superior to single treatments with FGFR and PI3K inhibitors, especially with BEZ235, for MB cell lines.


Asunto(s)
Meduloblastoma/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Humanos , Meduloblastoma/patología , Inhibidores de Proteínas Quinasas/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
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