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1.
Life Sci ; 234: 116756, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419444

RESUMO

AIMS: Conventional radiotherapy is mainly restricted by the low radiation absorption efficiency of tumors tissues and the hypoxic tumor cells radio-resistance. In this paper, novel nano-radiosensitizers, magnetic nanoparticles core coated with silica, were successfully prepared to overcome these limitations. MAIN METHODS: The prepared nanoparticles have been characterized by transmission electron microscope (TEM), Dynamic light scattering (DLS), atomic force microscope (AFM) and vibration sample magnetometer (VSM). MTT cytotoxicity and DNA double-strand breaks (Comet) assays have been used to assess the radio-enhancing effect of iron oxide magnetic nanoparticles (IO-MNPs) and silica-coated iron oxide magnetic nanoparticles (SIO-MNPs) against MCF7 breast cancer cells. MCF7 cells were treated with different concentrations of the prepared nanoformulations and exposed to an electron beam at doses 0, 0.5, 1, 2, 4 Gy. KEY FINDINGS: DLS measurements revealed that the main hydrodynamic diameter of the prepared IO-MNPs and SIO-MNPs was 18.17 ±â€¯4.5 nm and 164.18 ±â€¯16.1 nm, respectively, which was confirmed by TEM micrographs. MTT and comet assays results showed that the radiosensitizing effect of the prepared nanoformulations was dose and concentration dependent. Interestingly, the dose enhancement factor (DEF) for SIO-MNPs was, on average, 1.3-fold greater than that of IO-MNPs. SIGNIFICANCE: Coating of IO-MNPs with silica led to enhance their electron radiosensitization and consequently their therapeutic efficacy. Therefore, SIO-MNPs represent a promising engineered nano-formulation for enhancing breast cancer radiosensitivity.


Assuntos
Neoplasias da Mama/radioterapia , Compostos Férricos/uso terapêutico , Nanopartículas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Dióxido de Silício/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos da radiação , Dano ao DNA/efeitos da radiação , Elétrons , Feminino , Compostos Férricos/química , Humanos , Células MCF-7 , Nanopartículas/química , Radiossensibilizantes/química , Dióxido de Silício/química
2.
Chem Biol Interact ; 311: 108789, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31401089

RESUMO

The cytotoxicity of a dinuclear imine-copper (II) complex 2, and its analogous mononuclear complex 1, toward different melanoma cells, particularly human SKMEL-05 and SKMEL-147, was investigated. Complex 2, a tyrosinase mimic, showed much higher activity in comparison to complex 1, and its reactivity was verified to be remarkably activated by UVB-light, while the mononuclear compound showed a small or negligible effect. Further, a significant dependence on the melanin content in the tumor cells, both from intrinsic pigmentation or stimulated by irradiation, was observed in the case of complex 2. Similar tests with keratinocytes and melanocytes indicated a much lower sensitivity to both copper (II) complexes, even after exposition to UV light. Clonogenic assays attested that the fractions of melanoma cells survival were much lower under treatment with complex 2 compared to complex 1, both with or without previous irradiation of the cells. The process also involves generation of reactive oxygen species (ROS), as verified by EPR spectroscopy, and by using fluorescence indicators. Autophagic assays indicated a remarkable formation of cytoplasmic vacuoles in melanomas treated with complex 2, while this effect was not observed in similar treatment with complex 1. Monitoring of specific protein LC3 corroborated the simultaneous occurrence of autophagy. A balance interplay between different modes of cell death, apoptosis and autophagy, occurs when melanomas were treated with the dinuclear complex 2, in contrast to the mononuclear complex 1. These results pointed out to different mechanisms of action of such complexes, depending on its nuclearity.


Assuntos
Complexos de Coordenação/química , Cobre/química , Iminas/química , Monofenol Mono-Oxigenase/metabolismo , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Complexos de Coordenação/metabolismo , Complexos de Coordenação/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos da radiação , Humanos , Melaninas/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tubulina (Proteína)/metabolismo , Raios Ultravioleta
3.
Chem Commun (Camb) ; 55(67): 9971-9974, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31367709

RESUMO

Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses light, oxygen and a photosensitizer to produce localized reactive oxygen species (ROS). Due to the short lifetime of ROS, the location of the photosensitizer in the cell is believed to be the key determinant governing the outcome of PDT. To explore the effect of direct association between a photosensitizer and DNA a well know DNA-binding dye, DAPI, was converted into a photosensitizer. Br-DAPI - unlike native DAPI - upon irradiation produces ROS. We demonstrate that the ROS are only effective in inducing dsDNA breaks when Br-DAPI is bound to DNA. In cancer cells (A549) Br-DAPI causes rapid light dependent cell death. This work supports the design of photosensitizers which bind with high affinity to the DNA of target cells for potentially more effective PDT.


Assuntos
Bromo/química , DNA/química , Indóis/química , Fármacos Fotossensibilizantes/química , Células A549 , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Corantes Fluorescentes/química , Humanos , Luz , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Estudo de Prova de Conceito , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo
4.
J Photochem Photobiol B ; 197: 111504, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31228687

RESUMO

High disappointment rate of the ligament to hard tissue mending after the medical procedure has dependably been a testing issue in rotator cuff repair. Considering the elasticity of carbon dot decorated polyethylene (f-CDs-PE) and osteogenic movement of gold substituted hydroxyapatite (Au@HA) bioceramic, f-CDs-PE-Au@HA biocomposite coatings were created by an electrophoretic deposition method (EPD), the in vivo and in vitro bioactivity and cytocompatibility were researched. The physico-chemical properties of f-CDs-PE-Au@HA biocomposite coatings were characterized using fourier transform infra-red (FTIR) and X-Ray diffractometery (XRD). The morphology of the fabricated biocomposites was analyses via scanning electron microscopy (SEM) and transmission electron microscopy (TEM) methods. With a gamma-irradiation of f-CDs-PE-Au@HA biocomposite coating (BC2), the bond and multiplication of cells on biocomposite coating were improved. The specimen with a f-CDs-PE-Au@HA biocomposite (BC2) demonstrated a most noteworthy alkaline phosphatase activity articulation. The animal model consequences additionally show that the f-CDs-PE-Au@HA biocomposite (BC2) had great bioactive and cytocompatibility, which could develop the association of collagen and the arrangement of ligament and hard tissue. Expansion of the gamma-ray irradiation with f-CDs-PE-Au@HA biocomposite coating (BC2) at the tendon- hard tissue crossing point was exhibited to reinforce the mending entheses, increment hard tissue and tendon development and progress collagen association contrasted and control. The above outcomes have recommended that the progressive, implantable and solid stringy platforms built utilizing EPD extraordinary potential for enlargement of rotator cuff tears-recuperating.


Assuntos
Materiais Revestidos Biocompatíveis/química , Durapatita/química , Raios gama , Pontos Quânticos/química , Articulação do Ombro/patologia , Titânio/química , Artroplastia de Substituição , Densidade Óssea/efeitos da radiação , Carbono/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Materiais Revestidos Biocompatíveis/farmacologia , Colágeno Tipo I/metabolismo , Ouro/química , Humanos , Polietileno/química , Próteses e Implantes , Articulação do Ombro/diagnóstico por imagem , Tomografia Computadorizada por Raios X
5.
J Photochem Photobiol B ; 196: 111512, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129505

RESUMO

Cancer is a leading cause of death worldwide, and doxorubicin (DOX) has become one of the most commonly prescribed drugs. Stem cell (SC) therapy is proving to be a promising strategy to alleviate DOX adverse effects on non-cancerous cells. However, the drug also has a toxic action on SCs, reducing the efficiency of cell therapy from a preventive view. The present study shows that the DOX toxicity in mesenchymal SCs (MSCs) can be partially overcome by low-level laser irradiation (LLLI). To achieve this, we applied the low-level red laser (wavelength: 660 nm; output power: 30 mW; laser beam: 0.028 cm2; irradiation: 1.07 mW/cm2; Ga-Al-As Photon Laser III, DMC, São Paulo, Brazil) in rat adipose tissue-derived MSCs before their exposure to different DOX concentrations. Results revealed that the DOX reduced the viability and adenosine triphosphate level of MSCs. These findings were followed by significantly increased apoptosis as well as oxidative stress in the MSCs. Interestingly, LLLI at the dose of 0.2 J alleviated the effects of DOX on cell viability and apoptosis, and inhibited oxidative stress in the MSCs. In summary, this study provides a crucial step toward the future application of LLLI as a protective approach against DOX-induced toxicity in MSCs, particularly cell death. This study also lays the groundwork for further investigation into the role of oxidative stress and inflammation as an instructive milieu for cell protection.


Assuntos
Apoptose/efeitos da radiação , Doxorrubicina/farmacologia , Lasers , Trifosfato de Adenosina/metabolismo , Tecido Adiposo/citologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Citocinas/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Ratos
6.
Molecules ; 24(9)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31035502

RESUMO

The application of natural plant extracts in UV-protection is popular and intensively studied. Silymarin (from Silibum marianum), a naturally occurring polyphenol, has recently received attention due to its antioxidant, anti-inflammatory and anti-apoptotic effects. However, its role in the UV-mediated keratinocyte cell response is still controversial. In this study, we investigated the effects of Silibum marianum extracts with different origins and formulations on UVA-exposed HaCaT keratinocytes in vitro. Our results show, that silymarin treatment caused an inverse dose-dependent photosensitivity relationship (at higher doses, a decrease in cell viability and ROS production) after UVA exposure. The attenuation of the UVA-induced ROS generation after silymarin treatment was also observed. Moreover, silymarin pre-treatment increased the cyclobutane pyrimidine dimer photolesions in keratinocytes after UVA exposure. These results indicated the dual role of silymarin in UVA-exposed keratinocytes. It scavenges ROS but still induces phototoxicity. Based on our results dermatological applications of silymarin and related compounds should be considered very carefully.


Assuntos
Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Silimarina/química , Silimarina/farmacologia , Raios Ultravioleta , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Raios Ultravioleta/efeitos adversos
7.
Int J Mol Sci ; 20(9)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31035468

RESUMO

Traditional photodynamic therapy (PDT) is limited by the penetration depth of visible light. Although the light source has been changed to near infrared, infrared light is unable to overcome the penetration barrier and it is only effective at the surface of the tumors. In this study, we used X-ray as a light source for deep-seated tumor treatment. A particle with a narrow band gap when exposed to soft X-rays would produce reactive oxygen species (ROS) to kill tumor cell, with less damage to the normal tissues. Anatase TiO2 has been studied as a photosensitizer in PDT. In the experiment, C was doped into the anatase lattice at an optimum atomic ratio to make the band gap narrower, which would be activated by X-ray to produce more ROS and kill tumor cells under stress. The results showed that the synthesized TiO2:C particles were identified as crystal structures of anatase. The synthesized particles could be activated effectively by soft X-rays to produce ROS, to degrade methylene blue by up to 30.4%. Once TiO2:C was activated by X-ray irradiation, the death rate of A549 cells in in vitro testing was as high as 16.57%, on day 2. In the animal study, the tumor size gradually decreased after treatment with TiO2:C and exposure to X-rays on day 0 and day 8. On day 14, the tumor declined to nearly half of its initial volume, while the tumor in the control group was twice its initial volume. After the animal was sacrificed, blood, and major organs were harvested for further analysis and examination, with data fully supporting the safety of the treatment. Based on the results of the study, we believe that TiO2:C when exposed to X-rays could overcome the limitation of penetration depth and could improve PDT effects by inhibiting tumor growth effectively and safely, in vivo.


Assuntos
Carbono/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Titânio/química , Raios X , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Fármacos Fotossensibilizantes/farmacologia , Análise Espectral , Distribuição Tecidual , Titânio/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Nanoscale ; 11(18): 9185-9193, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31038146

RESUMO

Recent advances in nanotechnology have developed a lot of opportunities for biological applications. In this work, multifunctional MoS2/AuNR nanocomposites with unique high NIR absorption were designed via combining MoS2 nanosheets and gold nanorods (AuNRs). The nanocomposites were synthesized through electrostatic self-assembly and showed high stability and good biocompatibility. Then they were used to modulate the aggregation of amyloid-ß peptides, destabilize mature fibrils under NIR irradiation, and eliminate Aß-induced ROS against neurotoxicity. The inhibition and destabilization effects were confirmed by Thioflavin T (ThT) fluorescence assay and transmission electron microscopy (TEM). Cell viability assay and ROS assay revealed that MoS2/AuNR nanocomposites could alleviate Aß-induced oxidative stress and cell toxicity. More importantly, both MoS2 nanosheets and AuNRs can be used as NIR photothermal agents, MoS2/AuNR nanocomposites have enhanced ability of disrupting Aß fibrils and improved cell viability by generating local heat under low power NIR irradiation. Our results provide new insights into the design of new multifunctional systems for the treatment of amyloid-related diseases.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Raios Infravermelhos , Nanocompostos/química , Fragmentos de Peptídeos/metabolismo , Amiloide/química , Amiloide/toxicidade , Peptídeos beta-Amiloides/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dissulfetos/química , Ouro/química , Humanos , Molibdênio/química , Nanocompostos/toxicidade , Nanotubos/química , Fragmentos de Peptídeos/química , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier
9.
Molecules ; 24(9)2019 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31060229

RESUMO

Background: KDM5 enzymes are H3K4 specific histone demethylases involved in transcriptional regulation and DNA repair. These proteins are overexpressed in different kinds of cancer, including breast, prostate and bladder carcinomas, with positive effects on cancer proliferation and chemoresistance. For these reasons, these enzymes are potential therapeutic targets. Methods: In the present study, we analyzed the effects of three different inhibitors of KDM5 enzymes in MCF-7 breast cancer cells over-expressing one of them, namely KDM5B/JARID1B. In particular we tested H3K4 demethylation (western blot); radio-sensitivity (cytoxicity and clonogenic assays) and damage accumulation (COMET assay and kinetics of H2AX phosphorylation). Results: we show that all three compounds with completely different chemical structures can selectively inhibit KDM5 enzymes and are capable of increasing sensitivity of breast cancer cells to ionizing radiation and radiation-induced damage. Conclusions: These findings confirm the involvement of H3K4 specific demethylases in the response to DNA damage, show a requirement of the catalytic function and suggest new strategies for the therapeutic use of their inhibitors.


Assuntos
Neoplasias da Mama/enzimologia , Histona Desmetilases/antagonistas & inibidores , Histona Desmetilases com o Domínio Jumonji/genética , Proteínas Nucleares/genética , Radiossensibilizantes/farmacologia , Proteínas Repressoras/genética , Bibliotecas de Moléculas Pequenas/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Histonas/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/metabolismo , Células MCF-7 , Modelos Moleculares , Estrutura Molecular , Proteínas Nucleares/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/química , Proteínas Repressoras/metabolismo , Bibliotecas de Moléculas Pequenas/química , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/efeitos da radiação
10.
Int J Mol Sci ; 20(9)2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083373

RESUMO

Liquid crystal displays (LCDs) are used as screens in consumer electronics and are indispensable in the modern era of computing. LCDs utilize light-emitting diodes (LEDs) as backlight modules and emit high levels of blue light, which may cause retinal photoreceptor cell damage. However, traditional blue light filters may decrease the luminance of light and reduce visual quality. We adjusted the emitted light spectrum of LED backlight modules in LCDs and reduced the energy emission but maintained the luminance. The 661W photoreceptor cell line was used as the model system. We established a formula of the ocular energy exposure index (OEEI), which could be used as the indicator of LCD energy emission. Cell viability decreased and apoptosis increased significantly after exposure to LCDs with higher emitted energy. Cell damage occurred through the induction of oxidative stress and mitochondrial dysfunction. The molecular mechanisms included activation of the NF-κB pathway and upregulation of the expression of proteins associated with inflammation and apoptosis. The effect was correlated with OEEI intensity. We demonstrated that LCD exposure-induced photoreceptor damage was correlated with LCD energy emission. LCDs with lower energy emission may, therefore, serve as suitable screens to prevent light-induced retinal damage and protect consumers' eye health.


Assuntos
Luz , Cristais Líquidos/química , Células Fotorreceptoras de Vertebrados/patologia , Células Fotorreceptoras de Vertebrados/efeitos da radiação , Animais , Apoptose/efeitos da radiação , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos da radiação , Inflamação/patologia , Camundongos , Mitocôndrias/patologia , Mitocôndrias/efeitos da radiação , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos da radiação , Exposição à Radiação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos da radiação
11.
BMC Musculoskelet Disord ; 20(1): 193, 2019 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31054572

RESUMO

BACKGROUND: Cartilage repair outcomes are compromised in a pro-inflammatory environment; therefore, the mitigation of pro-inflammatory responses is beneficial. Treatment with continuous low-intensity ultrasound (cLIUS) at the resonant frequency of 5 MHz is proposed for the repair of chondral fissures under pro-inflammatory conditions. METHODS: Bovine osteochondral explants, concentrically incised to create chondral fissures, were maintained under cLIUS (14 kPa (5 MHz, 2.5 Vpp), 20 min, 4 times/day) for a period of 28 days in the presence or absence of cytokines, interleukin-6 (IL-6) or tumor necrosis factor (TNF)α. Outcome assessments included histological and immunohistochemical staining of the explants; and the expression of catabolic and anabolic genes by qRT-PCR in bovine chondrocytes. Cell migration was assessed by scratch assays, and by visualizing migrating cells into the hydrogel core of cartilage-hydrogel constructs. RESULTS: Both in the presence and absence of cytokines, higher percent apposition along with closure of fissures were noted in cLIUS-stimulated explants as compared to non-cLIUS-stimulated explants on day 14. On day 28, the percent apposition was not significantly different between unstimulated and cLIUS-stimulated explants exposed to cytokines. As compared to non-cLIUS-stimulated controls, on day 28, cLIUS preserved the distribution of proteoglycans and collagen II in explants despite exposure to cytokines. cLIUS enhanced the cell migration irrespective of cytokine treatment. IL-6 or TNFα-induced increases in MMP13 and ADAMTS4 gene expression was rescued by cLIUS stimulation in chondrocytes. Under cLIUS, TNFα-induced increase in NF-κB expression was suppressed, and the expression of collagen II and TIMP1 genes were upregulated. CONCLUSION: cLIUS repaired chondral fissures, and elicited pro-anabolic and anti-catabolic effects, thus demonstrating the potential of cLIUS in improving cartilage repair outcomes.


Assuntos
Cartilagem Articular/lesões , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Terapia por Ultrassom/métodos , Cicatrização/efeitos da radiação , Animais , Cartilagem Articular/citologia , Cartilagem Articular/patologia , Cartilagem Articular/efeitos da radiação , Bovinos , Técnicas de Cultura de Células , Movimento Celular/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Condrócitos/metabolismo , Osteocondrite/patologia , Osteocondrite/terapia , Cultura Primária de Células
12.
J Photochem Photobiol B ; 194: 84-95, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30933875

RESUMO

Ultraviolet (UV)-B radiation is a major environmental risk factor that is responsible for the development and progression of many skin cancers. Apigenin, a type of bioflavonoid, has been reported to inhibit UVB-induced skin cancer. However, how apigenin functions in keratinocytes with UV damage remains unclear. In this study, by lactate dehydrogenase (LDH) release assay, we found that apigenin treatment increased cell death in the primary human epidermal keratinocytes (HEKs) and the cutaneous squamous cell carcinoma cell line COLO-16. Apigenin treatment reduced microtubule-associated protein 1 light chain 3 (LC3)-II turnover, acridine orange staining and GFP-LC3 puncta in both cell types, suggesting autophagy inhibition. However, apigenin treatment restored the inhibition of autophagy in UVB-challenged HEKs. Moreover, apigenin treatment restored the UVB-induced downregulation of ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia, Rad3-related (ATR) and the unfolded protein response (UPR) regulatory proteins, BiP, IRE1α and PERK in HEKs. Apigenin treatment also inhibited UVB-induced apoptosis and cell death in HEKs. In addition, autophagy inhibition by autophagy-related gene (ATG) 5 RNA interference interrupted apigenin-induced restoration of ATR, ATM and BiP, which were downregulated in HEKs exposed to UVB radiation. Our findings indicate that apigenin exhibits a novel protective effect in keratinocytes with UVB damage, suggesting potential application as a photoprotective agent.


Assuntos
Apigenina/farmacologia , Autofagia/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Autofagia/efeitos da radiação , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Regulação para Baixo/efeitos da radiação , Células HEK293 , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Protetores contra Radiação/farmacologia , Resposta a Proteínas não Dobradas/efeitos da radiação
13.
J Photochem Photobiol B ; 194: 166-173, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30981089

RESUMO

Ultraviolet (UV) light exposure-induced photoaging of the skin is a multifactorial process involving both extrinsic and intrinsic cellular mechanisms. Several naturally occurring products are known to confer protection against UV light-induced skin damage. Our preliminary studies confirmed that the ethyl acetate fraction of coffee silverskin exhibits inhibitory effects on matrix metalloproteases (MMPs). Furthermore, we previously isolated and identified atractyligenin, which has MMP-inhibitory activity, from the silverskin ethyl acetate fraction. The aim of this study was to elucidate the anti-photoaging effects of atractyligenin on human dermal fibroblasts and the underlying mechanism. Human dermal fibroblasts were exposed to 8 J/cm2 UVA radiation, and cell viability was analyzed by MTT assay. The fluorescent dye 2', 7'-dichlorodihydrofluorescein diacetate (H2DCF-DA) was used to measure the intracellular reactive oxygen species (ROS) levels. Our study showed that atractyligenin significantly suppressed the expression of UVA-induced MMPs by inhibiting intracellular ROS production. Atractyligenin treatment reduced c-Jun phosphorylation and c-Fos expression by inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway activated by UVA irradiation. Additionally, treatment with atractyligenin contributed to the homeostasis of collagen by restoring the loss of collagen absorption-related receptor Endo180 and altered fibroblast morphology induced by UVA irradiation. These results indicate that atractyligenin isolated from coffee silverskin inhibits multiple pathways in the human skin photoaging process and is thus a potential candidate for treatment or prevention of photoaging.


Assuntos
Atractilosídeo/análogos & derivados , Café/química , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Atractilosídeo/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/efeitos da radiação , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Metaloproteinases da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo
14.
IET Nanobiotechnol ; 13(1): 58-65, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30964039

RESUMO

Electroporation facilitates loading of cells with molecules and substances that are normally membrane impermeable. Flow cytometry is used in this study to examine the effects of the application of electroporation-level monopolar electric field pulses of varying electrical field strength on Ishikawa endometrial adenocarcinoma cells. Analysis of the fluorescence versus forward scatter plots corroborates the well-recognised threshold and cell size dependence characteristics of electroporation, but also shows the progression of cell lysis and generation of particulate material. Two 500 µs monopolar rectangular pulses ranging from 1.0 × 105 to 2.5 × 105 V/m were used to electroporate the cells. Electroporation yields (fraction of viable cells exhibiting significant propidium iodide uptake) ranged from 0 to 97%, with viability ranging between 78 and 34% over the electric field strength range tested. The higher electric field strength pulses not only reduced cell viability, but also generated a substantial amount of sub-cellular sized particulate material indicating cells have been physically disrupted enough to create these particles.


Assuntos
Sobrevivência Celular/fisiologia , Sobrevivência Celular/efeitos da radiação , Eletroporação/métodos , Citometria de Fluxo/métodos , Linhagem Celular Tumoral , Tamanho Celular , Humanos
15.
Artif Cells Nanomed Biotechnol ; 47(1): 1416-1422, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31012327

RESUMO

Loss of the capacities of epidermal stem cells (ESCs) induced by ultraviolet-B (UV-B) irradiation has been widely associated with various skin diseases. Netrin-1, a member of the axonal guidance protein family, has displayed diverse biological functions in different types of cells and tissues, mediated by its specific receptor UNC-5 homolog B (UNC5b). In this study, we examined the physiological functions of netrin-1 and UNC5b in ESCs upon UV-B exposure. Our results indicate that UNC5b is expressed in ESCs, and its expression is upregulated in response to UV-B radiation. We found that treatment with netrin-1 prevented UV-B radiation-induced oxidative stress by reducing the generation of reactive oxygen species (ROS) and expression of NADPH oxidase 4 (NOX-4). Additionally, treatment with netrin-1 improved UV-B radiation-induced mitochondrial dysfunction by increasing mitochondrial membrane potential (MMP) levels and adenosine triphosphate (ATP) production. The presence of netrin-1 attenuated UV-B radiation-induced lactic dehydrogenase (LDH) release. UV-B exposure resulted in the loss of the capacities of ESCs by reducing the expressions of integrin ß1 and Krt19, the two major ESC markers. Importantly, this process was prevented by netrin-1. Silencing of UNC5b abolished the effects of netrin-1 on the expression of integrin ß1 and Krt19, suggesting that the effects of netrin-1 in maintaining the capacities of ESCs are dependent on UNC5b. Mechanistically, we found that the Wnt/ß-catenin signalling may be involved. Our findings suggest that netrin-1 may serve as a therapeutic agent for the treatment of skin diseases.


Assuntos
Células Epidérmicas/citologia , Netrina-1/farmacologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/efeitos da radiação , Raios Ultravioleta , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Netrina/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo
16.
Int J Mol Med ; 43(6): 2499-2506, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31017257

RESUMO

Photoaging is a consequence of chronic exposure to ultraviolet (UV) radiation and results in skin damage. In this study, whether tyndallizate of the probiotic bacterium Lactobacillus acidophilus IDCC 3302 (ACT 3302) can protect against UVB­induced photodamage to the skin was investigated. For this, HaCaT keratinocytes were used as a model for skin photoaging. HaCaT cells were treated with ACT 3302 prior to UVB exposure and skin hydration factors and matrix metalloproteinase (MMP)­1, MMP­2, and MMP­9 levels in the culture supernatant were evaluated by ELISA. The protective effects of ACT 3302 against UVB­induced oxidative stress in HaCaT cells was also assessed by measuring superoxide dismutase and catalase activity and detecting the expression of pro­inflammatory cytokine­encoding genes and mitogen­activated protein kinase (MAPK) signaling components by reverse transcription­quantitative polymerase chain reaction and western blotting, respectively. UVB exposure increased MMP expression and MAPK activation; these changes were attenuated by pretreatment with ACT 3302. Treatment with ACT 3302 prior to UVB exposure also attenuated inflammation. These results demonstrate that tyndallized ACT 3302 can mitigate photodamage to the skin induced by UVB radiation through the suppression of MMPs and could therefore be used clinically to prevent wrinkle formation.


Assuntos
Queratinócitos/efeitos da radiação , Lactobacillus acidophilus , Probióticos/farmacologia , Envelhecimento da Pele , Raios Ultravioleta/efeitos adversos , Linhagem Celular , Sobrevivência Celular/efeitos da radiação , Humanos , Queratinócitos/patologia , Lactobacillus acidophilus/citologia , Estresse Oxidativo/efeitos da radiação , Fatores de Proteção , Envelhecimento da Pele/patologia
17.
Biomed Pharmacother ; 112: 108656, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30970507

RESUMO

Radiotherapy is an adjuvant treatment of surgery in prostate cancer, while radioresistance has been the challenge of treatment. It has been reported that α-Solanine exhibits anti-cancer activity and enhances the chemo- and radio-sensitivity in several human cancers, whereas the role of α-Solanine on radiosensitivity to PCa remains to be uncovered yet. We found α-Solanine decreased cell viability in human PCa cells rather than normal prostate epithelial cells in vitro. Functional experiments showed that cell viability and colonies formation were declined & apoptosis rate and DNA double strand breaks (DSBs) marker γ-H2AX expressions were elevated by α-Solanine in PCa cells treated with X-ray irradiation, compared with X-ray irradiation treatment only. GAS5 was down-regulated & miR-18a was up-regulated in PCa cells, which was reversed in the presence of α-Solanine. Effects of ectopic GAS5 on inhibiting cell viability and survival & promoting apoptosis and DNA damage were reversed by miR-18a overexpression in PCa cells. Moreover, GAS5 regulated miR-18a expression by target binding during α-Solanine treatment. Collectively, α-Solanine suppresses cell proliferation and promotes radiosensitivity through up-regulating GAS5/miR-18a pathway in PCa. Our results provide a novel mechanism of α-Solanine treatment in human prostate cancer and help to develop a new approach to sensitizing radioresistant prostate cancer cells by targeting GAS5/miR-18a.


Assuntos
Proliferação de Células/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , RNA Longo não Codificante/genética , Tolerância a Radiação/genética , Radiossensibilizantes/farmacologia , Solanina/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Sobrevivência Celular/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Masculino , Neoplasias da Próstata/patologia , Tolerância a Radiação/efeitos dos fármacos , Tolerância a Radiação/efeitos da radiação , Raios X
18.
Chemistry ; 25(45): 10633-10641, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31025784

RESUMO

A new class of luminescent molecular hybrids in which eight cyclometalated iridium(III) polypyridine complexes are grafted onto a polyhedral oligomeric silsesquioxane (POSS) unit [POSS-{Ir(N^C)2 (py-im)}8 ](PF6 )8 [py-im=pyridine imine; HN^C=N-phenylpyrazole (Hppz) (1 a), 2-phenylpyridine (Hppy) (2 a), 2-phenylquinoline (Hpq) (3 a)] were synthesized and characterized. On photoexcitation, the complexes showed intense and long-lived orange-red to red emission in fluid solutions at room temperature and in low-temperature glasses. The photophysical properties including aggregation-induced emission and biological properties of these complexes were studied and compared with those of their POSS-free counterparts [Ir(N^C)2 (py-im)](PF6 ) [HN^C=Hppz (1 b), Hppy (2 b), Hpq (3 b)]. The (photo)cytotoxicity of the complexes was examined by the MTT assay, and their cellular uptake and intracellular localization were investigated by inductively coupled plasma-mass spectrometry and laser-scanning confocal microscopy.


Assuntos
Complexos de Coordenação/síntese química , Irídio/química , Compostos de Organossilício/química , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Células HeLa , Humanos , Espectrometria de Massas , Microscopia Confocal , Nanoestruturas/química , Piridinas/química , Raios Ultravioleta
19.
Bull Exp Biol Med ; 166(6): 785-787, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31028581

RESUMO

We studied the effect of low and high-dose rate photon radiation on activation of cell death by apoptosis and necrosis in malignant cell lines of lymphocytic origin Raji and Jurkat (human B and T-cell lymphomas) and normal human lymphocytes from healthy volunteers. It was shown that photon radiation with ultra-high dose rate induced significantly higher levels of "early" apoptosis and lower levels of necrosis compared to γ-radiation with dose rate used for radiation therapy.


Assuntos
Apoptose/efeitos da radiação , Raios gama , Linfócitos/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Relação Dose-Resposta à Radiação , Humanos , Células Jurkat , Linfócitos/patologia , Necrose/patologia , Cultura Primária de Células
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