RESUMO
Corilagin (CLG) is a hydrolyzable tannin and possesses various pharmacological activities. Here, we investigated the impact of CLG as an anti-tumor agent against human gastric tumor cells. We observed that CLG could cause negative regulation of JAKs-Src-STAT3/5 signaling axis in SNU-1 cells, but did not affect these pathways in SNU-16 cells. Interestingly, CLG promoted the induction of mitogen-activated protein kinases (MAPKs) signaling pathways in only SNU-16 cells, but not in the SNU-1 cells. CLG exhibited apoptotic effects that caused an increased accumulation of the cells in sub-G1 phase and caspase-3 activation in both SNU-1 and SNU-16 cell lines. We also noticed that CLG and docetaxel co-treatment could exhibit significantly enhanced apoptotic effects against SNU-1 cells. Moreover, the combinations treatment of CLG and docetaxel markedly inhibited cell growth, phosphorylation of JAK-Src-STAT3 and induced substantial apoptosis. Additionally, pharmacological inhibition of JNK, p38, and ERK substantially blocked CLG-induced activation of MAPKs, cell viability, and apoptosis, thereby implicating the pivotal role of MAPKs in the observed anti-cancer effects of CLG. Taken together, our data suggest that CLG could effectively block constitutive STAT3/5 activation in SNU-1 cells but induce sustained MAPKs activation in SNU-16 cells.
Assuntos
Proteínas Quinases Ativadas por Mitógeno , Neoplasias Gástricas , Apoptose , Linhagem Celular Tumoral , Docetaxel/farmacologia , Glucosídeos , Humanos , Taninos Hidrolisáveis/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias Gástricas/tratamento farmacológicoRESUMO
PURPOSE: Lycopus lucidus Turcz (LLT) is a potent traditional medicinal herb that exerts therapeutic effects, regulating inflammatory disorders. However, the precise mechanisms by which LLT plays a potent role as an anti-inflammatory agent are still unknown, and in particular, the effects of LLT on cortical neurons and related mechanisms of neuroinflammation have not been studied. The NLRP3 inflammasome pathway is one of the most well known as an important driver of inflammation. We therefore hypothesized that LLT, as an effective anti-inflammatory agent, might have neurotherapeutic potential by inhibiting the NLRP3 inflammasome pathway in cortical neurons. MATERIALS AND METHODS: Primary cortical neurons were isolated from the embryonic rat cerebral cortex, and H2O2 was used to stimulate neuron damage in vitro. After treatment with LLT at three concentrations (10, 25, and 50 µg/mL), the expression of iNOS, NLRP3, ASC, caspase-1, IL-1ß, IL-18, IL-6, and IL-10 was determined by immunocytochemistry, qPCR, and ELISA. Neuron apoptosis was also evaluated using Annexin V-FITC/PI double staining FACS analysis. Neural regeneration-related factors (BDNF, NGF, synaptophysin, NT3, AKT, and mTOR) were analyzed by immunocytochemistry and qPCR. RESULTS: LLT effectively protected cultured rat cortical neurons from H2O2-induced neuronal injury by significantly inhibiting NLRP3 inflammasome activation. In addition, it significantly reduced caspase-1 activation, which is induced by inflammasome formation and regulated the secretion of IL-1ß/IL-18. We demonstrated that LLT enhances axonal elongation and synaptic connectivity upon H2O2-induced neuronal injury in rat primary cortical neurons. CONCLUSION: It was first demonstrated in vitro that LLT suppresses NLRP3 inflammasome activation, attenuates inflammation and apoptosis, and consequently promotes neuroprotection and the stimulation of neuron repair, suggesting that it is a promising therapeutic for neurological diseases.
RESUMO
Inula britannica var. chinensis (IBC) has been used as a traditional medicinal herb to treat inflammatory diseases. Although its anti-inflammatory and anti-oxidative effects have been reported, whether IBC exerts neuroprotective effects and the related mechanisms in cortical neurons remain unknown. In this study, we investigated the effects of different concentrations of IBC extract (5, 10, and 20 µg/mL) on cortical neurons using a hydrogen peroxide (H2O2)-induced injury model. Our results demonstrate that IBC can effectively enhance neuronal viability under in vitro-modeled reaction oxygen species (ROS)-generating conditions by inhibiting mitochondrial ROS production and increasing adenosine triphosphate level in H2O2-treated neurons. Additionally, we confirmed that neuronal death was attenuated by improving the mitochondrial membrane potential status and regulating the expression of cytochrome c, a protein related to cell death. Furthermore, IBC increased the expression of brain-derived neurotrophic factor and nerve growth factor. Furthermore, IBC inhibited the loss and induced the production of synaptophysin, a major synaptic vesicle protein. This study is the first to demonstrate that IBC exerts its neuroprotective effect by reducing mitochondria-associated oxidative stress and improving mitochondrial dysfunction.
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Brassinin (BSN), a precursor of phytoalexins, extracted from Chinese cabbage has been reported to act as a promising anti-neoplastic agent. However, the effects of BSN on colon cancer cells and its underlying mechanisms have not been fully elucidated. This study aimed at investigating the anti-neoplastic impact of BSN and its possible synergistic effect with paclitaxel on colon cancer cells. The effect of BSN on Janus-activated kinases (JAKs)/signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways and its downstream functions was deciphered using diverse assays in colon carcinoma cells. We found that BSN displayed significant cytotoxic effect and suppressed cell proliferation on colon carcinoma cells. Additionally, it was noted that BSN modulated oncogenic gene expression and induced apoptosis through down regulating multiple oncogenic signaling cascades such as JAKs/STAT3 and PI3K/Akt/mTOR simultaneously. Besides, BSN-paclitaxel combination significantly increased cytotoxicity and induced apoptosis synergistically as compared with individual treatment of both the agents. Overall, our findings indicate that BSN may be a novel candidate for anti-colon cancer targeted therapy.
Assuntos
Neoplasias do Colo , Indóis/farmacologia , Paclitaxel , Transdução de Sinais/efeitos dos fármacos , Tiocarbamatos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Humanos , Paclitaxel/farmacologia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TORRESUMO
Protocatechuic acid (PA) is widely distributed and commonly occurring natural compound that can exert antioxidant, anti-inflammatory, as well as anti-cancer effects. Epithelial-to-mesenchymal transition (EMT) is important cellular process that can control tumor invasion and metastasis. Here, we investigated whether PA can modulate the EMT process in basal and transforming growth factorß-induced A549 and H1299 cells. We found that PA suppressed expression of mesenchymal markers (Fibronectin, Vimentin, and N-cadherin), MMP-9, MMP-2, twist, and snail but stimulated the levels of epithelial markers (E-cadherin and Occludin). In addition, PA can affect TGFß-induced expression of both mesenchymal and epithelial markers. Moreover, PA abrogated migratory and invasive potential of tumor cells by reversing the EMT process. Furthermore, we found that PA suppressed EMT process by abrogating the activation of PI3K/Akt/mTOR signaling cascade in lung cancer cells.
Assuntos
Anticarcinógenos/química , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Hidroxibenzoatos/química , Neoplasias Pulmonares/tratamento farmacológico , Proliferação de Células , Humanos , Neoplasias Pulmonares/patologia , Transdução de Sinais , TransfecçãoRESUMO
Lung cancer is the largest cause of cancer-induced deaths. Non-small cell lung cancer (NSCLC) is the most frequently observed subtype of lung cancer. Although recent studies have provided many therapeutic options, there is still a need for effective and safe treatments. This paper reports the combined effects of cinnamaldehyde (CNM), a flavonoid from cinnamon, together with hyperthermia, a therapeutic option for cancer treatment, on the A549 NSCLC cell line. A hyperthermia treatment of 43 °C potentiated the cytotoxicity of CNM in A549 cells. This was attributed to an increase in the apoptosis markers and suppression of the survival/protective factors, as confirmed by Western blot assays. Flow cytometry supported this result because the apoptotic profile, cell health profile, and cell cycle profile were regulated by CNM and hyperthermia combination therapy. The changes in reactive oxygen species (ROS) and its downstream target pathway, mitogen-activated protein kinases (MAPK), were evaluated. The CNM and hyperthermia combination increased the generation of ROS and MAPK phosphorylation. N-acetylcysteine (NAC), a ROS inhibitor, abolished the apoptotic events caused by CNM and hyperthermia co-treatment, suggesting that the cytotoxic effect was dependent of ROS signaling. Therefore, we suggest CNM and hyperthermia combination as an effective therapeutic option for the NSCLC treatment.
Assuntos
Acroleína/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Hipertermia Induzida/métodos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Pulmonares/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células A549 , Acetilcisteína/farmacologia , Acroleína/farmacologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/terapia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosforilação/efeitos dos fármacosRESUMO
According to the World Health Organization (WHO), cancer is the second-highest cause of mortality in the world, and it kills nearly 9.6 million people annually. Besides the fatality of the disease, poor prognosis, cost of conventional therapies, and associated side-effects add more burden to patients, post-diagnosis. Therefore, the search for alternatives for the treatment of cancer that are safe, multi-targeted, effective, and cost-effective has compelled us to go back to ancient systems of medicine. Natural herbs and plant formulations are laden with a variety of phytochemicals. One such compound is rhein, which is an anthraquinone derived from the roots of Rheum spp. and Polygonum multiflorum. In ethnomedicine, these plants are used for the treatment of inflammation, osteoarthritis, diabetes, and bacterial and helminthic infections. Increasing evidence suggests that this compound can suppress breast cancer, cervical cancer, colon cancer, lung cancer, ovarian cancer, etc. in both in vitro and in vivo settings. Recent studies have reported that this compound modulates different signaling cascades in cancer cells and can prevent angiogenesis and progression of different types of cancers. The present review highlights the cancer-preventing and therapeutic properties of rhein based on the available literature, which will help to extend further research to establish the chemoprotective and therapeutic roles of rhein compared to other conventional drugs. Future pharmacokinetic and toxicological studies could support this compound as an effective anticancer agent.
Assuntos
Antraquinonas/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Fallopia multiflora/química , Neoplasias , Raízes de Plantas/química , Rheum/química , Antraquinonas/química , Antineoplásicos Fitogênicos/química , Feminino , Humanos , Masculino , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/prevenção & controleRESUMO
Theacrine, a purine alkaloid structurally similar to caffeine, has recently become of interest as a potential therapeutic compound. Here, we investigated the antimetastatic potential of theacrine on human breast cancer MDA-MB-231 cells. We observed that theacrine can reverse epithelial-to-mesenchymal transition (EMT), which resulted in a decrease in the levels of mesenchymal markers (Fibronectin, Vimentin, N-cadherin, Twist, and Snail) and an increase in the levels of epithelial markers (Occludin and E-cadherin) in the cells. Additionally, theacrine attenuates TGF-ß-induced EMT, cell adhesion, migration, and invasion in MDA-MB-231 cells. Overall, our results suggest that theacrine may inhibit the breast cancer cell metastasis by reversing the EMT process.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Ácido Úrico/análogos & derivados , Neoplasias da Mama/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Feminino , Fibronectinas/metabolismo , Humanos , Proteínas Nucleares/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Proteína 1 Relacionada a Twist/metabolismo , Ácido Úrico/farmacologia , Vimentina/metabolismoRESUMO
Although application of sorafenib in the treatment of human renal cell carcinoma (RCC) remains one of the best examples of successful targeted therapy, majority of RCC patients suffer from its side effects as well as develop resistance to this targeted therapy. Thus, there is a need to promote novel alternative therapies for the treatment of RCC. In this study, we investigated whether Korean red ginseng extract (KRGE) could inhibit the proliferation and induce chemosensitization in human renal cancer cells. Also, we used a human phospho-antibody array containing 46 antibodies against signaling molecules to examine a subset of phosphorylation events after KRGE and sorafenib combination treatment. Korean red ginseng extract suppressed the proliferation of two RCC cell lines; activated caspase-3; caused poly(ADP-ribose) polymerase cleavage; abrogated the expression of B-cell lymphoma 2, B-cell lymphoma extra large, survivin, inhibitors of apoptosis proteins-1/2, cyclooxygenase-2, cyclin D1, matrix metallopeptidase-9, and vascular endothelial growth factor; and upregulated pro-apoptotic gene products. Interestingly, KRGE enhanced the cytotoxic and apoptotic effects of sorafenib in RCC cells. The combination treatment of KRGE and sorafenib more clearly suppressed cyclic adenosine monophosphate response element-binding protein and c-Jun phosphorylation and induced phosphorylation of p53 than did the individual treatment regimen. Our results clearly demonstrate that KRGE can enhance the anticancer activity of sorafenib and may have a substantial potential in the treatment of RCC. Copyright © 2017 John Wiley & Sons, Ltd.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Niacinamida/análogos & derivados , Panax/química , Compostos de Fenilureia/farmacologia , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-jun/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Humanos , Niacinamida/farmacologia , Fosforilação , Sorafenibe , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy. We determined the anti-tumor mechanism of GAC 17:1 with respect to its effect on STAT3 signaling pathway in multiple myeloma cell lines. We found that GAC 17:1 can inhibit constitutive activation of STAT3 through the abrogation of upstream JAK2, Src but not of JAK1 kinases in U266 cells and also found that GAC can suppress IL-6-induced STAT3 phosphorylation in MM.1S cells. Treatment of protein tyrosine phosphatase (PTP) inhibitor blocked suppression of STAT3 phosphorylation by GAC 17:1, thereby indicating a critical role for a PTP. We also demonstrate that GAC 17:1 can induce the substantial expression of PTEN and SHP-1 at both protein and mRNA level. Further, deletion of PTEN and SHP-1 genes by siRNA can repress the induction of PTEN and SHP-1, as well as abolished the inhibitory effect of drug on STAT3 phosphorylation. GAC 17:1 down-regulated the expression of STAT3 regulated gene products and induced apoptosis of tumor cells. Overall, GAC 17:1 was found to abrogate STAT3 signaling pathway and thus exert its anticancer effects against multiple myeloma cells.
Assuntos
Ginkgo biloba/química , PTEN Fosfo-Hidrolase/metabolismo , Extratos Vegetais/farmacologia , Folhas de Planta/química , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Fator de Transcrição STAT3/agonistas , Salicilatos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Ligação Proteica , Salicilatos/químicaRESUMO
A principal limitation to the clinical use of cisplatin is the high incidence of chemoresistance to this drug. Combination treatments with other drugs may help to circumvent this problem. Wogonin, one of the major natural flavonoids, is known to reverse multidrug resistance in several types of cancers. We investigated the ability of wogonin to overcome cisplatin resistance in head and neck cancer (HNC) cells and further clarified its molecular mechanisms of action. Two cisplatin-resistant HNC cell lines (AMC-HN4R and -HN9R) and their parental and other human HNC cell lines were used. The effects of wogonin, either alone or in combination with cisplatin, were assessed in HNC cells and normal cells using cell cycle and death assays and by measuring cell viability, reactive oxygen species (ROS) production, and protein expression, and in tumor xenograft mouse models. Wogonin selectively killed HNC cells but spared normal cells. It inhibited nuclear factor erythroid 2-related factor 2 and glutathione S-transferase P in cisplatin-resistant HNC cells, resulting in increased ROS accumulation in HNC cells, an effect that could be blocked by the antioxidant N-acetyl-L-cysteine. Wogonin also induced selective cell death by targeting the antioxidant defense mechanisms enhanced in the resistant HNC cells and activating cell death pathways involving PUMA and PARP. Hence, wogonin significantly sensitized resistant HNC cells to cisplatin both in vitro and in vivo. Wogonin is a promising anticancer candidate that induces ROS accumulation and selective cytotoxicity in HNC cells and can help to overcome cisplatin-resistance in this cancer.
Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Flavanonas/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Fator 2 Relacionado a NF-E2/genética , Animais , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Scutellaria baicalensis/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is persistently activated in squamous cell carcinoma of the head and neck (SCCHN) and can cause uncontrolled cellular proliferation and division. HYPOTHESIS: Thus, its targeted abrogation could be an effective strategy to reduce the risk of SCCHN. Resveratrol is known for its anti-cancer efficacy in a variety of cancer models. STUDY DESIGN: The effect resveratrol on STAT3 activation, associated protein kinases, phosphatases, cellular proliferation and apoptosis was investigated. METHODS: We evaluated the effect of resveratrol on STAT3 signaling cascade and its regulated functional responses in SCCHN cells. RESULTS: We found that HN3 and FaDu cells expressed strongly phosphorylated STAT3 on both tyrosine 705 and serine 727 residues as compared to other SCCHN cells. The phosphorylation was completely suppressed by resveratrol in FaDu cells, but not substantially in HN3 cells. STAT3 suppression was mediated through the inhibition of activation of upstream JAK2, but not of JAK1 and Src kinases. Treatment with the protein tyrosine phosphatase (PTP) inhibitor pervanadate reversed the resveratrol-induced down-regulation of STAT3, thereby indicating a critical role for a PTP. We also found that resveratrol induced the expression of the SOCS-1 protein and mRNA. Further, deletion of SOCS-1 gene by siRNA suppressed the induction of SOCS-1, and reversed the inhibition of STAT3 activation. Resveratrol down-regulated various STAT3-regulated gene products, inhibited proliferation, invasion, as well as induced the cell accumulation in the sub-G1 phase and caused apoptosis. Beside, this phytoalexin also exhibited the enhancement of apoptosis when combined with ionizing radiation treatment. CONCLUSION: Our results suggest that resveratrol blocks STAT3 signaling pathway through induction of SOCS-1, thus attenuating STAT3 phosphorylation and proliferation in SCCHN cells.
Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Radiossensibilizantes/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologia , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Humanos , Janus Quinase 1/metabolismo , Janus Quinase 2/metabolismo , Fosforilação/efeitos dos fármacos , Resveratrol , Fator de Transcrição STAT3/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteína 1 Supressora da Sinalização de Citocina , Quinases da Família src/metabolismoRESUMO
Ginkgetin, a biflavone from Ginkgo biloba leaves, is known to exhibit antiinflammatory, antifungal, neuroprotective, and antitumor activities, but its precise mechanism of action has not been fully elucidated. Because the aberrant activation of STAT3 has been linked with regulation of inflammation, proliferation, invasion, and metastasis of tumors, we hypothesized that ginkgetin modulates the activation of STAT3 in tumor cells. We found that ginkgetin clearly suppressed constitutive phosphorylation of STAT3 through inhibition of the activation of upstream JAK1 and c-Src kinases and nuclear translocation of STAT3 on both A549 and FaDu cells. Treatment with sodium pervanadate reversed the ginkgetin-induced down-modulation of STAT3, thereby indicating a critical role for a PTP. We also found that ginkgetin strongly induced the expression of the SHP-1 and PTEN proteins and its mRNAs. Further, deletion of SHP-1 and PTEN genes by siRNA suppressed the induction of SHP-1 and PTEN, and reversed the inhibition of STAT3 activation. Ginkgetin induced apoptosis as characterized by an increased accumulation of cells in subG1 phase, positive Annexin V binding, loss of mitochondrial membrane potential, down-regulation of STAT3-regulated gene products, and cleavage of PARP. Overall, ginkgetin abrogates STAT3 signaling pathway through induction of SHP-1 and PTEN proteins, thus attenuating STAT3 phosphorylation and tumorigenesis.
Assuntos
Apoptose/efeitos dos fármacos , Biflavonoides/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Proteína Tirosina Quinase CSK , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Humanos , Janus Quinase 1/metabolismo , Fosforilação , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Quinases da Família src/metabolismoRESUMO
Embelin (EB) is a benzoquinone derivative isolated from Embelia ribes Burm plant. Recent scientific evidence shows that EB induces apoptosis and inhibits migration and invasion in highly metastatic human breast cancer cells. However, the exact mechanisms of EB in tumor metastasis and invasion have not been fully elucidated. Here, we investigated the underlying mechanisms of antimetastatic activities of EB in breast cancer cells. The EB downregulated the chemokine receptor 4 (CXCR4) as well as matrix metalloproteinase (MMP)-9/2 expression and upregulated the tissue inhibitor of metalloproteinase 1 expression in MDA-MB-231 cells under noncytotoxic concentrations but not in MCF-7 cells. Additionally, EB inhibited the CXC motif chemokine ligand 12 induced invasion and migration activities of MDA-MB-231 cells. A detailed study of underlying mechanisms revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by the downregulation of mRNA expression and suppression of nuclear factor-kappa B (NF-κB) activation. It further reduced the binding of NF-κB to the CXCR4 promoter. Besides, EB downregulated mesenchymal marker proteins (neural cadherin and vimentin) and concurrently upregulated epithelial markers (epithelial cadherin and occludin). Overall, these findings suggest that EB can abrogate breast cancer cell invasion and metastasis by suppression of CXCR4, MMP-9/2 expressions, and inhibition of epithelial-mesenchymal transition and thus may have a great potential to suppress metastasis of breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Benzoquinonas/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Receptores CXCR4/metabolismo , Benzoquinonas/administração & dosagem , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Feminino , Humanos , Células MCF-7 , Invasividade Neoplásica , Transdução de Sinais , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
INTRODUCTION: The purpose of this study was to investigate the efficacy of a 1440-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser on relieving pain in relation to the levels of inflammatory cytokine and neuropeptides in the root canal exudates of teeth with persistent symptomatic apical periodontitis. METHODS: Forty teeth with persistent symptomatic apical periodontitis were randomly assigned to treatment groups: group L, intracanal irradiation of 1440-nm Nd:YAG laser with a 300-µm-diameter fiberoptic tip in addition to conventional root canal retreatment, and group C, conventional root canal re-treatment. The degrees of both spontaneous pain and the pain on percussion before and after treatment were recorded, and root canal exudate samples were collected to quantify the associated levels of substance P, calcitonin gene-related peptide (CGRP), and matrix metalloproteinase (MMP)-8 by immunoassay. RESULTS: All of the measured parameters were significantly reduced in group L (P < .05), whereas the level of pain on percussion, CGRP, and MMP-8 were significantly reduced in group C (P < .05). The 1440-nm Nd:YAG laser had significantly better effect on the relief of pain on percussion and the reduction of substance P, CGRP, and MMP-8 levels. The visual analog scale scores of perceived pain correlated with pain-related neuropeptides and inflammatory cytokine levels in root canal exudates. CONCLUSIONS: The 1440-nm Nd:YAG laser irradiation via fiberoptic tip to the teeth with persistent apical periodontitis provided promising consequences of pain and inflammation modulation.
Assuntos
Cavidade Pulpar/efeitos da radiação , Lasers de Estado Sólido/uso terapêutico , Terapia com Luz de Baixa Intensidade/instrumentação , Neuropeptídeos/efeitos da radiação , Dor/radioterapia , Periodontite Periapical/radioterapia , Adulto , Peptídeo Relacionado com Gene de Calcitonina/efeitos da radiação , Citocinas/efeitos da radiação , Exsudatos e Transudatos/efeitos da radiação , Feminino , Seguimentos , Humanos , Mediadores da Inflamação/efeitos da radiação , Masculino , Metaloproteinase 8 da Matriz/efeitos da radiação , Pessoa de Meia-Idade , Neurotransmissores/efeitos da radiação , Fibras Ópticas , Medição da Dor/métodos , Percussão , Estudos Prospectivos , Retratamento , Substância P/efeitos da radiação , Vasodilatadores/efeitos da radiaçãoRESUMO
Exposure experiments were conducted to determine the effects of an oil spill on a periphytic microbial community with the chemically enhanced water-accommodated fraction (CEWAF) of Iranian Heavy Crude oil in a microcosm containing artificial benthic substrates. Bacteria and heterotrophic nano-flagellates (HNF) grew well in all the treatments, except for the 100% CEWAF exposure. However, periphyton did not adapt to concentrations of CEWAF ≥ 20%. Among the periphyton, Cylindrotheca spp. dominated under treatment conditions, and the response of Cylindrotheca spp. to CEWAF (i.e., particularly 10%) closely followed the changes in chlorophyll a concentration. The concentrations of petroleum hydrocarbons from 10% and 20% CEWAF seemed to have a negative effect on periphyton and a growth-promoting effect on bacteria and HNF, respectively.
Assuntos
Biofilmes/efeitos dos fármacos , Petróleo/toxicidade , Microbiologia da Água , Bactérias/efeitos dos fármacos , Ecossistema , Fungos/efeitos dos fármacos , Irã (Geográfico) , Modelos Biológicos , Modelos Químicos , Poluição por PetróleoRESUMO
INTRODUCTION: The purpose of this study was to investigate the efficacy of laser-activated irrigation (LAI) of 1320-nm neodymium-doped:yttrium-aluminum-garnet (Nd:YAG) laser on sealer penetration into dentinal tubules in the presence of 5.25% sodium hypochlorite (NaOCl) or 17% ethylenediaminetetraacetic acid (EDTA). METHODS: The curved root canals (>20°) from 63 extracted human molars (negative control, n = 3) were prepared to size #30.06 with NaOCl irrigation. Teeth were divided into 4 groups (n = 15) as follows: group N, NaOCl irrigation without LAI; group E, EDTA irrigation without LAI; group NL, LAI with NaOCl; group EL, LAI with EDTA. In all groups, the laser fiber was inserted and withdrawn 4 times for 5 seconds each. Teeth were obturated with gutta-percha and fluorescent-labeled sealer. Transverse sections at 2 and 5 mm from root apex were examined with confocal laser scanning microscopy, and the percentage of sealer penetration into dentinal tubules was measured. RESULTS: Groups E, NL, and EL showed higher percentage of sealer penetration than group N (P < .05). With NaOCl as irrigant, LAI (group NL) resulted in significantly higher amount of sealer penetration than nonactivated group (group N) in both levels (P < .05). However, with EDTA, no significant differences in sealer penetration were observed between the laser-activated group (group EL) and its nonactivated counterpart (group E) in both levels (P > .05). CONCLUSIONS: The 1320-nm Nd:YAG laser activation with either NaOCl or EDTA was much better than NaOCl irrigation alone and as effective as EDTA final flush for sealer penetration into dentinal tubules. Additional use of laser with EDTA did not improve the quality of obturation in the curved canals.
Assuntos
Cavidade Pulpar/ultraestrutura , Dentina/ultraestrutura , Lasers de Estado Sólido/uso terapêutico , Materiais Restauradores do Canal Radicular/uso terapêutico , Irrigantes do Canal Radicular/uso terapêutico , Quelantes/efeitos da radiação , Quelantes/uso terapêutico , Ácido Edético/efeitos da radiação , Ácido Edético/uso terapêutico , Resinas Epóxi/química , Resinas Epóxi/uso terapêutico , Corantes Fluorescentes , Guta-Percha/química , Guta-Percha/uso terapêutico , Humanos , Umidade , Microscopia Confocal , Dente Molar , Materiais Restauradores do Canal Radicular/química , Irrigantes do Canal Radicular/efeitos da radiação , Obturação do Canal Radicular/métodos , Preparo de Canal Radicular/instrumentação , Preparo de Canal Radicular/métodos , Hipoclorito de Sódio/efeitos da radiação , Hipoclorito de Sódio/uso terapêutico , Temperatura , Irrigação Terapêutica/métodos , Fatores de TempoRESUMO
INTRODUCTION: The purpose of this study was to evaluate the effects of endodontic irrigants on the push-out strength and hydration behavior of accelerated mineral trioxide aggregate (MTA) in its early setting phase. METHODS: In an in vitro perforation model, MTA with or without 10% CaCl(2) was condensed and allowed to initial set for 10 minutes. The samples were divided into four groups (n = 10) to be immersed into either 3.5% sodium hypochlorite (NaOCl) or 2% chlorhexidine gluconate (CHX) for 30 minutes and then allowed to set for 48 hours. In the control group, a wet cotton pellet was placed over MTA. The maximum force applied to the set MTA mixture before dislodgement was recorded. Irrigant-treated surfaces were examined using a scanning electron microscope (SEM). Chemical elements of these surfaces were also analyzed by energy dispersive x-ray spectroscope (EDS). RESULTS: The push-out strength of group A1 (NaOCl-treated accelerated MTA) was the highest of all groups. When compared with nonaccelerated MTA, CaCl(2)-accelerated MTA showed significantly higher push-out strength (p < 0.05). NaOCl-treated groups showed significantly higher push-out strength than CHX-treated groups (p < 0.05). Scanning electron microscopic examination and EDS analysis showed that the formation of calcium hydroxide crystals on accelerated MTA exposed to NaOCl was increased compared with those of the control group. CONCLUSION: These findings imply that the use of accelerated MTA under the NaOCl irrigation was effective in perforation repair without altering its hydration behavior even in the early setting phase.