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1.
Int J Mol Sci ; 22(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34445559

RESUMO

Scutellarein (SCU) is a well-known flavone with a broad range of biological activities against several cancers. Human hepatocellular carcinoma (HCC) is major cancer type due to its poor prognosis even after treatment with chemotherapeutic drugs, which causes a variety of side effects in patients. Therefore, efforts have been made to develop effective biomarkers in the treatment of HCC in order to improve therapeutic outcomes using natural based agents. The current study used SCU as a treatment approach against HCC using the HepG2 cell line. Based on the cell viability assessment up to a 200 µM concentration of SCU, three low-toxic concentrations of (25, 50, and 100) µM were adopted for further investigation. SCU induced cell cycle arrest at the G2/M phase and inhibited cell migration and proliferation in HepG2 cells in a dose-dependent manner. Furthermore, increased PTEN expression by SCU led to the subsequent downregulation of PI3K/Akt/NF-κB signaling pathway related proteins. In addition, SCU regulated the metastasis with EMT and migration-related proteins in HepG2 cells. In summary, SCU inhibits cell proliferation and metastasis in HepG2 cells through PI3K/Akt/NF-κB signaling by upregulation of PTEN, suggesting that SCU might be used as a potential agent for HCC therapy.


Assuntos
Apigenina/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , NF-kappa B/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Movimento Celular , Proliferação de Células , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , NF-kappa B/genética , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Células Tumorais Cultivadas
2.
Nutrients ; 12(8)2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32824273

RESUMO

Sinensetin (SIN) has been reported to exhibit anti-inflammatory and anti-cancer activity. However, the cellular and molecular mechanism by which SIN promotes hepatocellular carcinoma (HCC) cell death remains unclear. In the present study, we investigated the induction of cell death by SIN and its underlying mechanism in HepG2 cells, an HCC cell line. We found that SIN significantly induced cell death in HepG2 cells, whereas the proliferation rate of Thle2, human liver epithelial cells, was unaffected by SIN. SIN-treated HepG2 cells were not affected by apoptotic cell death; instead, autophagic cell death was induced through the p53-mediated AMPK/mTOR signaling pathway. Inhibition of p53 degradation led to both autophagy and apoptosis in HepG2 cells. p53 translocation led to SIN-induced autophagy, whereas p53 translocation inhibited SIN-induced apoptosis. However, SIN showed apoptosis in the p53-mutant Hep3B cell line. Molecular docking simulation of the p53 core domain showed effective binding with SIN, which was found significant compared with the known p53 activator, RITA. Collectively, these data suggest that SIN may be a potential anti-cancer agent targeting autophagic cell death in human liver cancer.


Assuntos
Antineoplásicos/farmacologia , Morte Celular Autofágica/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Flavonoides/farmacologia , Neoplasias Hepáticas/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Simulação de Acoplamento Molecular/métodos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/metabolismo
3.
Oncol Rep ; 44(3): 939-958, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32705238

RESUMO

Scutellarein (SCU), a flavone that belongs to the flavonoid family and abundantly present in Scutellaria baicalensis a flowering plant in the family Lamiaceae, has been reported to exhibit anticancer effects in several cancer cell lines including gastric cancer (GC). Although our previous study documented the mechanisms of Scutellarein­induced cytotoxic effects, the literature shows that the proteomic changes that are associated with the cellular response to SCU have been poorly understood. To avoid adverse side­effects and significant toxicity of chemotherapy in patients who react poorly, biomarkers anticipating therapeutic responses are imperative. In the present study, we utilized a comparative proteomic analysis to identify proteins associated with Scutellarein (SCU)­induced cell death in GC cells (AGS and SNU484), by integrating two­dimensional gel electrophoresis (2­DE), mass spectrometry (MS), and bioinformatics to analyze the proteins. Proteomic analysis between SCU­treated and DMSO (control) samples successfully identified 41 (AGS) and 31 (SNU484) proteins by MALDI­TOF/MS analysis and protein database search. Comparative proteomics analysis between AGS and SNU484 cells treated with SCU revealed a total of 7 protein identities commonly expressed and western blot analysis validated a subset of identified critical proteins, which were consistent with those of the 2­DE outcome. Molecular docking studies also confirmed the binding affinity of SCU towards these critical proteins. Phosphatidylinositol 4,5­bisphosphate 3­kinase catalytic subunit ß isoform (PIK3CB) protein expression was accompanied by a distinct group of cellular functions, including cell growth, and proliferation. Cancerous inhibitor of protein phosphatase 2A (CIP2A), is one of the oncogenic molecules that have been shown to promote tumor growth and resistance to apoptosis and senescence­inducing therapies. In the present study, both PIK3CB and CIP2A proteins were downregulated in SCU­treated cells, which boosts our previous results of SCU to induce apoptosis and inhibits GC cell growth by regulating these critical proteins. The comparative proteomic analysis has yielded candidate biomarkers of response to SCU treatment in GC cell models and further validation of these biomarkers will help the future clinical development of SCU as a novel therapeutic drug.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apigenina/farmacologia , Biomarcadores Tumorais/genética , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Apigenina/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Autoantígenos/análise , Autoantígenos/genética , Autoantígenos/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Classe I de Fosfatidilinositol 3-Quinases/análise , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/análise , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Simulação de Acoplamento Molecular , Mapas de Interação de Proteínas/efeitos dos fármacos , Proteômica , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
4.
Am J Chin Med ; 48(3): 679-702, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32329644

RESUMO

Autophagy is a process of active programmed cell death, where a dying cell induces autophagosomes and subsequently regulated by degradative machinery. The aim of this study was to investigate the mechanism behind induction of autophagic cell death by Naringin flavonoid in AGS cancer cells. Growth inhibition of AGS cells showed downregulation of PI3K/Akt/mTOR signaling by Naringin treatment. Transmission electron microscopy observation showed swollen mitochondria and lysosome near peri-nuclear zone fused with autophagic vacuoles. Rapamycin pre-treatment with Naringin showed significant decrease in mTOR phosphorylation and increase in LC3B activation in AGS cells. Decrease in mTOR phosphorylation is associated with lysosomal function activation was observed by time-dependent treatment of Naringin. Induction of lysosomal membrane permeabilization (LMP) was observed by LAMP1 activation leading lysosomal cell death by releasing Cathepsin D from lysosomal lumen to cytosol. Naringin treated AGS cells showed up-regulating BH3 domain Bad, down-regulating Bcl-xL, and Bad phosphorylation and significant mitochondrial fluorescence intensity expression. Significant localization of mitochondria and LC3B activation was examined by person coefficient correlation. Activation of ERK1/2-p38 MAPKs and production of intracellular ROS has been observed over Naringin treatment. It has also been elucidated that pre-treatment with NAC inhibited mitochondria-LC3B colocalization, where ROS acted as upstream of ERK1/2-p38 MAPKs activation. Lysosomal cell death involvement has been evaluated by BAF A1 pre-treatment, inhibiting LAMP1, Cathepsin D, ROS, and blocking autophagolysosome in AGS cell death. Taken together, these findings show that, Naringin induced autophagy cell death involves LMP mediated lysosomal damage and BH3 protein Bad activation in AGS cancer cells.


Assuntos
Autofagia/efeitos dos fármacos , Flavanonas/farmacologia , Lisossomos/patologia , Neoplasias Gástricas/patologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Humanos , Lisossomos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Células Tumorais Cultivadas
5.
Int J Environ Health Res ; : 1-10, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191530

RESUMO

The toxicity of cadmium (Cd) occurs through accumulation in the environment. The precise mechanism underlying Cd toxicity remains unclear. Therefore, in the present study, we studied the effects of Cd on MM55.K cells and investigated the mechanisms underlying Cd-induced cell death. CdCl2 significantly elevated apoptotic cell death, mitochondrial membrane potential (ΔΨm) loss, and caspase-dependent cell death. Moreover, immunoblotting results revealed that CdCl2 down-regulated the inhibitor of apoptotic protein such as survivin and Bcl-2 which led to the activation of caspase-3 and the cleavage of PARP in MM55.K cells. Besides, CdCl2 caused the up-regulation of ROS-related proteins such as HO-1 and ER stress-related proteins such as GRP78 and CHOP in MM55.K cells. CdCl2 toxicity resulted in the down-regulation of the AKT pathway that leads to the up-regulation of phosphorylated JNK and p38 in MM55.K cells. Thus, CdCl2 induce toxicity by AKT/MAPK regulation and causing ROS production, ER stress, ΔΨm loss, and apoptotic cell death in normal mouse renal cells.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31781269

RESUMO

The use of adipose-derived stem cells (ADSCs) to enhance wound healing and tissue regeneration is progressively being accepted. Proteomic profiling of cultured ADSCs by mass spectrometry (MS) is a valuable tool to determine the identity of the proteins involved in multiple pathways, which make these ADSCs unique. In the current study, Nano-LC-MS/MS analysis was implemented on the membrane-free stem cell component (MFSCC), and the MS analysis revealed the presence of 252 proteins, that are involved in several biological functions, like metabolic process, biological regulation, developmental process, cell proliferation, and many more. Furthermore, bioinformatic analyses of the identified proteins in MFSCC found them to be involved in versatile pathways, like integrin pathway and wound healing response-related pathways. In addition, we also investigated the anti-inflammatory effects of MFSCC on lipopolysaccharide (LPS) stimulated mouse macrophage (RAW264.7) cells. The cell cytotoxicity of MFSCC was measured using MTT and LDH assays, the production of nitric oxide (NO) was measured by the Griess assay, and the protein expression levels of inducible nitric oxide (iNOS) and cyclooxygenase (COX-2) were examined by western blot analysis. The results showed that MFSCC concentrations ranging from 0.1 to 3 µg/mL did not show any significant cytotoxicity in LPS-induced RAW264.7 cells. Treatment with MFSCC of LPS-stimulated RAW264.7 cells significantly suppressed the production of NO and the expression of iNOS and COX-2 proteins related to inflammation. The present findings lead to a better understanding of the therapeutic potential of MFSCC and strongly promote it for the future clinical development of novel non-cell-based stem cell therapeutics.

7.
Int J Mol Sci ; 20(19)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31575035

RESUMO

Membrane-free stem cell components (MFSCC) from basal adipose tissue-derived stem cells (ADSCs) are unknown for the treatment strategies in osteoarthritis (OA). OA has been considered to be associated with inflammatory damage and cartilage degradation. In this study, we intended to investigate the molecular mechanism of the anti-inflammation and cartilage protection effect of MFSCC in vitro (rat primary chondrocytes) and in vivo (rat OA model). The MFSCC treatment significantly inhibited interleukin-1α (IL-1α) stimulated inflammation and cartilage degradation. The MFSCC considerably reduced the levels of inflammatory factors such as iNOS, COX-2, NO, and PGE2 and was suppressed NF-κB and MAPKs signaling pathways in IL-1α-stimulated rat chondrocytes. Additionally, biomarkers of OA such as MMP-9, COMP, and CTX-II decreased in the monosodium iodoacetate (MIA)-induced rat OA model by MFSCC treatment. In conclusion, the MFSCC was established to suppress IL-1α induced inflammation and cartilage degradation in vitro and in vivo. These findings provide new insight for understanding OA therapy using membrane-free stem cell approaches.


Assuntos
Cartilagem Hialina/metabolismo , Interleucina-1alfa/metabolismo , Osteoartrite/etiologia , Osteoartrite/metabolismo , Células-Tronco/metabolismo , Animais , Biomarcadores , Condrócitos/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoartrite/patologia , Ratos
8.
Sci Rep ; 9(1): 10029, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296948

RESUMO

The first 3-D direct observation of clusters of Nd oxide inside silicate glasses was achieved using atom probe tomography. Three-dimensional elemental maps of major chemical elements in glasses such as Si, Al, Zn and O showed no evidence of regions that had concentrations higher than the average values, whereas the Nd aggregated into regions of high concentration. Elemental maps of Nd and Pb recorded from the glasses containing PbS QDs showed highly-concentrated areas of both elements at the same locations; this result indicates that PbS QDs formation started in association with the Nd clusters.

9.
Int J Mol Med ; 43(1): 393-403, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30387810

RESUMO

To date, Korean hinoki cypress (Chamaecyparis obtusa), has been widely used for household and commercial purposes. Although the medicinal efficacy of hinoki cypress essential oil has been observed, that of the essential oil­derived terpenes, which exhibit a mechanism that acts against lung inflammation, remains to be fully elucidated. The present study investigated the anti­inflammatory effect of hinoki cypress leaf extracted essential oil on lipopolysaccharide (LPS)­stimulated WI38 fibroblast cells by inhibiting the nuclear factor κ­light­chain­enhancer of activated B cells (NF­κB) pathway, which exhibited lung tissue protection through the olfactory administration of essential oil in Sprague­Dawley rats. GC/MS analysis derived 24 terpenes from the essential oil. The morphological observations revealed that, upon LPS stimulation of WI38 fibroblast cells, inflammation was induced, whereas the condition of the cells reverted to normal in the essential oil extract pre­treated group. The results of western blot analysis revealed the inhibition of inducible nitric oxide synthase, activation of cyclooxygnase­2, and the degradation of cytosolic p65 and inhibitor of NF­κB­α in the LPS­stimulated group. Additionally, confocal imaging of nuclei revealed the translocation of phosphorylated p65, which was recovered in the cytosol in the phytoncide essential oil pre­treated group. Histopathological observation revealed that the alveolar capacity was enhanced in the essential oil olfactory administered rat group, compared with that in the normal rat group. These findings suggest that terpenes in essential oil from the Chamaecyparis obtusa leaf have therapeutic potential against respiratory inflammation­related disease.


Assuntos
Chamaecyparis/química , Fibroblastos/patologia , Inflamação/patologia , NF-kappa B/metabolismo , Óleos Voláteis/farmacologia , Folhas de Planta/química , Substâncias Protetoras/farmacologia , Respiração/efeitos dos fármacos , Administração por Inalação , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Fibroblastos/efeitos dos fármacos , Humanos , Lipopolissacarídeos , Masculino , Modelos Biológicos , Óxido Nítrico Sintase Tipo II/metabolismo , Óleos Voláteis/administração & dosagem , Substâncias Protetoras/administração & dosagem , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/patologia , Ratos Sprague-Dawley , Terpenos/análise
10.
Nutrients ; 10(11)2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30380781

RESUMO

Pectolinarigenin (PEC), a natural flavonoid that is present in citrus fruits, has been reported to exhibit antitumor effects in several cancers. Though the mechanism of PEC-induced cytotoxicity effects has been documented, the proteomic changes that are associated with the cellular response to this flavonoid are poorly understood in gastric cancer cells. In this study, a comparative proteomic analysis was performed to identify proteins associated with PEC-induced cell death in two human gastric cancer cell lines: AGS and MKN-28. Two-dimensional gel electrophoresis (2-DE) revealed a total of 29 and 56 protein spots with significant alteration were screened in AGS and MKN-28 cells respectively. In total, 13 (AGS) and 39 (MKN28) proteins were successfully identified by mass spectrometry from the differential spots and they are known to be involved in signal transduction, apoptosis, transcription and translation, cell structural organization, and metabolism, as is consistent with multiple effects of PEC on tumor cells. Notably, novel target proteins like Probable ATP-dependent RNA helicase DDX4 (DDX4) and E3 ubiquitin-protein ligase LRSAM1 (LRSAM1) along with the commonly differential expressed proteins on both the cell lines that are treated with PEC were confirmed by immunoblotting. The DDX4 accelerates cell cycle progression by abrogating the G2 checkpoint when overexpressed in cancer cells, while the aberrant expression of LRSAM1 may be involved in the cancer pathology. Thus, proteomic analysis provides vital information about target proteins that are important for PEC-induced cell death in gastric cancer cells.


Assuntos
Antineoplásicos/farmacologia , Cromonas/farmacologia , Proteínas de Neoplasias/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , RNA Helicases DEAD-box/efeitos dos fármacos , Eletroforese em Gel Bidimensional , Perfilação da Expressão Gênica , Humanos , Proteômica , Transdução de Sinais/efeitos dos fármacos , Ubiquitina-Proteína Ligases/efeitos dos fármacos
11.
Oncol Rep ; 40(6): 3249-3260, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30272339

RESUMO

Proteomic analysis serves as an important biological tool for identifying biological events. Novel biomarkers of a specific disease such as cancer may be identified using these promising techniques. The aim of the present study was to investigate the effect of tangeretin and to identify potential biomarkers in AGS gastric cancer cells using a proteomics approach. The results of the present study revealed that tangeretin inhibited AGS cell viability dose­dependently with a half­maximal inhibitory concentration of 100 µM. Two­dimensional gel electrophoresis was performed to determine the potential biomarker between control and tangeretin (100 µM)­treated AGS cells. A total of 16 proteins was identified from 36 significant protein spots using matrix­assisted laser­desorption/ionization time­of­flight­mass spectrometry using peptide fingerprinting. The bioinformatics tools Protein ANalysis THrough Evolutionary Relationships (PANTHER) and Database for Annotation, Visualization and Integrated Discovery (DAVID) were used to identify the functional properties and association of the proteins obtained. Using western blot analysis, the regulatory pattern of four selected proteins, protein kinase Cε, mitogen­activated protein kinase 4, phosphoinositide 4­kinase and poly(ADP­ribose) polymerase 14, were successfully verified in replicate sample sets. These selected proteins are primarily involved in apoptosis signaling, angiogenesis, cell cycle regulation, receptor kinase binding, intracellular cytoplasmic and nuclear alterations. Therefore, aim of the present study was to identify potential diagnostic biomarkers from the functional categories of altered protein expression in tangeretin­inhibited AGS gastric cancer cell viability.


Assuntos
Biomarcadores Tumorais/metabolismo , Flavonas/farmacologia , Proteômica/métodos , Neoplasias Gástricas/metabolismo , 1-Fosfatidilinositol 4-Quinase/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletroforese em Gel Bidimensional , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Mapas de Interação de Proteínas/efeitos dos fármacos , Proteína Quinase C-épsilon/metabolismo , Neoplasias Gástricas/tratamento farmacológico
12.
Nutrients ; 10(8)2018 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-30096805

RESUMO

Pectolinarigenin (PEC), a natural flavonoid present in Cirsium chanroenicum and in some species of Citrus fruits, has various pharmacological benefits such as anti-inflammatory and anti-cancer activities. In the present study, we investigated the anti-cancer mechanism of PEC induced cell death caused by autophagy and apoptosis in AGS and MKN28 human gastric cancer cells. The PEC treatment significantly inhibited the AGS and MKN28 cell growth in a dose-dependent manner. Further, PEC significantly elevated sub-G1 phase in AGS cells and G2/M phase cell cycle arrest in both AGS and MKN28 cells. Apoptosis was confirmed by Annexin V and Hoechst 33342 fluorescent staining. Moreover, Immunoblotting results revealed that PEC treatment down-regulated the inhibitor of apoptosis protein (IAP) family protein XIAP that leads to the activation of caspase-3 thereby cleavage of PARP (poly-ADP-ribose polymerase) in both AGS and MKN28 cells in a dose-dependent manner. The autophagy-inducing effect was indicated by the increased formation of acidic vesicular organelles (AVOs) and increased protein levels of LC3-II conversion in both AGS and MKN28 cells. PEC shows the down regulation of PI3K/AKT/mTOR pathway which is a major regulator of autophagic and apoptotic cell death in cancer cells that leads to the down-regulation of p-4EBP1, p-p70S6K, and p-eIF4E in PEC treated cells when compared with the untreated cells. In conclusion, PEC treatment might have anti-cancer effect by down-regulation of PI3K/AKT/mTOR pathway leading to G2/M phase cell cycle arrest, autophagic and apoptotic cell death in human gastric cancer cells. Further studies of PEC treatment can support to develop as a potential alternative therapeutic agent for human gastric carcinoma.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Cromonas/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Linhagem Celular Tumoral , Humanos , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia
13.
Oncotarget ; 9(5): 5993-6006, 2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29464049

RESUMO

Gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths worldwide. South Korea is in first place with 9,180 death alone attributed to gastric cancer in 2013. Plenty of literature suggests the evasion of apoptosis is implicated in neurodegeneration, autoimmune diseases, and tumors development due to dysregulation in the apoptotic mechanism. Reduced apoptosis or its resistance in cancer cells plays a significant role in carcinogenesis. It's imperative to understand apoptosis, which provides the basis for novel targeted therapies that can induce cancer cell death or sensitize them to cytotoxic agents by regulating key factors like IAPs, MDM2, p53, caspases and much more. Studies have demonstrated that Scutellarein have the ability to inhibit several cancer cells by inducing apoptosis with both: Scutellarein monomers as well as scutellarein containing flavonoids. MTT results revealed that scutellarein inhibited cell viability in both dose and time dependent manner. Flow cytometry and western blot analysis showed that scutellarein induces apoptosis in both AGS and SNU-484 human gastric cancer cells and G2/M phase cell cycle arrest in SNU-484 cells. This study demonstrated that the Scutellarein on AGS and SNU-484 cells significantly inhibits cell proliferation and induces apoptotic cell death via down regulating MDM2 and activated the tumor suppresser protein p53, subsequently down regulating the IAP family proteins (cIAP1, cIAP2, and XIAP) leading to caspase-dependent apoptosis in AGS and SNU-484 cells.

14.
Mol Med Rep ; 16(4): 5386-5392, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28849065

RESUMO

Protein array technology not only identifies a large number of proteins but also determines their expression levels. In the present study, antibody array analysis is used to decipher the proteins involved in hesperidin-induced cell death in HepG2 cells. Altered proteins in hesperidin treated cells were compared with that of untreated control cells by using a RayBio® Label­based (L series) human antibody array kit. The identified proteins were further confirmed using western blot analysis. STRING software based analysis was used to determine the protein­protein interactions. Many proteins related to signal transduction, cellular mechanisms, cell growth and proliferation regulatory proteins were identified. Among the proteins identified Hsp90, Smac/DIABLO, Prdx6 and FRK were significantly reduced in hesperidin treated cells. To the best of the authors' knowledge, the present study is the first to use antibody array for identifying proteins marker in hesperidin­induced cell death in HepG2 cells. The present study provides a novel insight into the anticancer mechanism of hesperidin.


Assuntos
Células Hep G2/efeitos dos fármacos , Células Hep G2/metabolismo , Hesperidina/farmacologia , Proteoma , Proteômica , Bases de Dados de Proteínas , Humanos , Análise Serial de Proteínas , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteômica/métodos
15.
Oncol Lett ; 14(1): 607-614, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28693212

RESUMO

Korean Scutellaria baicalensis Georgi has been widely used in Korean folk medicines for its range of medicinal benefits, including its anticancer effect. The aim of the present study was to investigate the underlying molecular mechanism of action of a flavonoid extract from Korean Scutellaria baicalensis Georgi (FSB) on AGS human gastric cancer cells (gastric adenocarcinoma) in which FSB exhibits an anticancer effect. Treatment of AGS cells with FSB significantly inhibited cell viability in a concentration-dependent manner. Furthermore, FSB significantly increased the proportion of cells in sub-G1 phase, and Annexin V and Hoechst 33258 fluorescent staining confirmed the apoptotic cell death. Furthermore, western blotting results identified that treatment of AGS cells with FSB significantly downregulated the expression of caspase family members, namely procaspases 3 and 9, and poly(ADP-ribose) polymerase (PARP), and subsequently upregulated cleaved caspase 3 and cleaved PARP. It was observed that FSB treatment significantly decreased the mitochondrial membrane potential of AGS cells. In addition, the ratio of the mitochondrion-associated proteins B cell lymphoma 2-associated X protein and B cell lymphoma extra large was upregulated. The results of the present study provide novel insight into the underlying molecular mechanism of the anticancer effects of FSB on AGS human gastric cancer cells and indicate that FSB may be an alternative chemotherapeutic agent for the treatment of gastric cancer.

16.
Radiat Oncol J ; 35(2): 185-188, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28712281

RESUMO

Primary liver tumor, especially hepatocellular carcinoma (HCC), is a common cause of cancer death worldwide. The incidence is generally higher in Asian countries than in western countries. Carcinogenesis of HCC is often associated with hepatitis viral infections. Current standard treatment of HCC is surgical resection or transplantation in patients with early stage disease. However, the patient with advanced stage disease, surgical resection is often limited. Sorafenib or other treatment modalities are not so effective as well. We report a case of unusual radiation super-sensitivity in advanced stage HCC, and review the literature.

17.
J Phys Ther Sci ; 29(6): 1113-1115, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28626338

RESUMO

[Purpose] The aim of this study was to analyze the effect of pain scrambler therapy on antineuralgic pain and quality of life after shingles. [Subjects and Methods] Daily pain scrambler therapy was administered to antineuralgic patients for 10 days, with each session lasting approximately 40 minutes. Pain was measured using the visual analog scale, and quality of life was assessed with the short form 36-item (SF-36). [Results] After10 sessions of pain scrambler therapy, pain had significantly reduced compared to that experienced prior to treatment. The quality of life had also improved following completion of 10 treatment sessions. [Conclusion] Pain scrambler therapy decreased patients' post-shingles antineuralgic pain and improved quality of life.

18.
Biomed Chromatogr ; 31(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28623844

RESUMO

The Korean Petasites japonicus is a perennial plant used in folk medicine as a remedy for many diseases and popularly consumed as spring greens. Ten polyphenols were characterized from the leaves, stems and roots of this plant via high-performance liquid chromatography-tandem mass spectrometry. Individual polyphenols were quantified for the first time using calibration curves of six structurally related external standards. Validation data indicated that coefficients of determinations (R2 ) were ≥0.9702 for all standards. Recoveries measured at 50 and 100 mg/L were 80.0-91.9 and 80.3-105.3%, respectively. Precisions at these two concentration levels were 0.7-6.1 and 1.1-5.5%, respectively. The total number of identified components was largest for the leaves and smallest for the stems. The leaf and root polyphenolic extracts showed anti-inflammatory effects by inducing LPS-activated COX-2 and iNOS protein levels in mouse macrophage RAW 264.7 cells. The antioxidant capacity of the polyphenols, when evaluated for DPPH (α,α-diphenyl-ß-picrylhydrazyl)ˑ , ABTS+ [2-2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] and superoxide radical scavenging activities, and in ferric reducing ability of plasma (FRAP) assays, was highest in the leaf and lowest in the stem. This trend suggests that the antioxidant capacities depend primarily on polyphenol concentration in each tissue. The current findings suggest that polyphenols derived from P. japonicas tissues could have potential as functional health foods.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Petasites/química , Extratos Vegetais/química , Polifenóis/farmacologia , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/metabolismo , Expressão Gênica/efeitos dos fármacos , Camundongos , Óxido Nítrico Sintase Tipo II/análise , Óxido Nítrico Sintase Tipo II/metabolismo , Polifenóis/química , Células RAW 264.7 , Espectrometria de Massas em Tandem/métodos
19.
Oncotarget ; 8(28): 46273-46285, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28545035

RESUMO

Hepatic steatosis is frequently observed in obese and aged individuals. Because hepatic steatosis is closely associated with metabolic syndromes, including insulin resistance, dyslipidemia, and inflammation, numerous efforts have been made to develop compounds that ameliorate it. Here, a novel peroxisome proliferator-activated receptor (PPAR) α agonist, 4-(benzo[d]thiazol-2-yl)benzene-1,3-diol (MHY553) was developed, and investigated its beneficial effects on hepatic steatosis using young and old Sprague-Dawley rats and HepG2 cells.Docking simulation and Western blotting confirmed that the activity of PPARα, but not that of the other PPAR subtypes, was increased by MHY553 treatment. When administered orally, MHY553 markedly ameliorated aging-induced hepatic steatosis without changes in body weight and serum levels of liver injury markers. Consistent with in vivo results, MHY553 inhibited triglyceride accumulation induced by a liver X receptor agonist in HepG2 cells. Regarding underlying mechanisms, MHY553 stimulated PPARα translocation into the nucleus and increased mRNA levels of its downstream genes related to fatty acid oxidation, including CPT-1A and ACOX1, without apparent change in lipogenesis signaling. Furthermore, MHY553 significantly suppresses inflammatory mRNA expression in old rats. In conclusion, MHY553 is a novel PPARα agonist that improved aged-induced hepatic steatosis, in part by increasing ß-oxidation signaling and decreasing inflammation in the liver. MHY553 is a potential pharmaceutical agent for treating hepatic steatosis in aging.


Assuntos
Envelhecimento/metabolismo , Ácidos Graxos/metabolismo , Fígado Gorduroso/metabolismo , Inflamação/metabolismo , Oxirredução , PPAR alfa/agonistas , Envelhecimento/patologia , Animais , Biomarcadores , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Metabolismo dos Lipídeos , Modelos Moleculares , Conformação Molecular , PPAR alfa/química , PPAR alfa/genética , Transporte Proteico , Ratos , Transcrição Genética
20.
Oncol Lett ; 13(4): 2521-2530, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28454429

RESUMO

Lonicera japonica Thunb. (L. japonica T.) has historically been used in Korean herbal medicine due to its anticancer and protective effects on the respiratory system. In the present study, the polyphenolic compounds in L. japonica T. were investigated using high-performance liquid chromatography coupled with tandem mass spectrometry, and its anticancer effects on A549 non-small-cell lung cancer cells were studied. Polyphenolic compounds potentially inhibit A549 cells in a dose-dependent manner. Flow cytometry and western blot analysis demonstrated that polyphenolic compounds induce apoptosis by regulating the protein expression levels of caspases, poly-(ADP-ribose) polymerase and the B-cell lymphoma-2-associated X-protein/B-cell lymphoma-extra large ratio. Furthermore, polyphenolic compounds inhibited mitochondrial membrane potential activity. Caspase-3 activity was increased in a dose-dependent manner and polyphenolic compounds inhibited the activation of protein kinase B by dephosphorylation. These results suggest that polyphenolic compounds in A549 cells indicate the anticancer activity through the induction of apoptosis.

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