Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445110

RESUMO

Epidermal growth factor receptor (EGFR) is overexpressed in lung cancer patients. Despite treatment with various EGFR tyrosine kinase inhibitors, recurrence and metastasis of lung cancer are inevitable. Docetaxel (DTX) is an effective conventional drug that is used to treat various cancers. Several researchers have studied the use of traditional herbal medicine in combination with docetaxel, to improve lung cancer treatment. SH003, a novel herbal mixture, exerts anticancer effects in different cancer cell types. Here, we aimed to investigate the apoptotic and anticancer effects of SH003 in combination with DTX, in human non-small-cell lung cancer (NSCLC). SH003, with DTX, induced apoptotic cell death, with increased expression of cleaved caspases and cleaved poly (ADP-ribose) polymerase in NSCLC cells. Moreover, SH003 and DTX induced the apoptosis of H460 cells via the suppression of the EGFR and signal transducer and activator of transcription 3 (STAT3) signaling pathways. In H460 tumor xenograft models, the administration of SH003 or docetaxel alone diminished tumor growth, and their combination effectively killed cancer cells, with increased expression of apoptotic markers and decreased expression of p-EGFR and p-STAT3. Collectively, the combination of SH003 and DTX may be a novel anticancer strategy to overcome the challenges that are associated with conventional lung cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Inibidores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
2.
Nutrients ; 13(3)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809267

RESUMO

Although the anti-obesity effect of Korean red ginseng (Panax ginseng Meyer) has been revealed, its underlying mechanisms are not clearly understood. Here, we demonstrate an involvement of gut microbiome in the inhibitory effect of Korean red ginseng on high-fat-diet (HFD)-induced mouse obesity, and further provides information on the effects of saponin-containing red ginseng extract (SGE) and saponin-depleted red ginseng extract (GE). Mice were fed with either SGE or GE every third day for one month, and their food intakes, fat weights, plasma glucose, and insulin and leptin levels were measured. Immunofluorescence assays were conducted to measure pancreatic islet size. Stools from the mice were subjected to metagenomic analysis. Both SGE and GE attenuated HFD-induced gain of body weight, reducing HFD-induced increase of food intakes and fat weights. They also reduced HFD-increased plasma glucose, insulin, and leptin levels, decreased both fasting and postprandial glucose concentrations, and improved both insulin resistance and glucose intolerance. Immunofluorescence assays revealed that they blocked HFD-induced increase of pancreatic islet size. Our pyrosequencing of the 16S rRNA gene V3 region from stools revealed that both SGE and GE modulated HFD-altered composition of gut microbiota. Therefore, we conclude that Korean red ginseng inhibits HFD-induced obesity and diabetes by altering gut microbiome.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal , Obesidade/tratamento farmacológico , Panax , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Animais , Glicemia/análise , Imunofluorescência , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Insulina/sangue , Leptina/sangue , Masculino , Metagenômica , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/microbiologia , Obesidade/patologia , Pâncreas/patologia , RNA Ribossômico 16S/genética
3.
Anticancer Res ; 40(12): 6835-6844, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33288575

RESUMO

BACKGROUND/AIM: Adhesion G protein-coupled receptors (aGPCRs) have a crucial role in cancer. However, the role of ADGRF4, one of aGPCRs, in cancer has yet to be revealed. Therefore, we investigated its role in lung cancer, a leading cause of cancer-related deaths worldwide. MATERIALS AND METHODS: ADGRF4 gene expression pattern in lung cancer were analyzed by in silico analyses. RNA sequencing was conducted to investigate gene expression pattern altered by ADGRF4 knockdown. Lung cancer cell lines were subjected to cell migration and invasion assays. RESULTS: In silico analysis data indicated a major role of ADGRF4 in lung cancer. RNA sequencing data showed that ADGRF4 gene silencing in lung cancer cells altered global expression pattern. ADGRF4 gene silencing reduced lung cancer cell invasiveness. Furthermore, PPP2C gene expression was most significantly down-regulated by ADGRF4 gene silencing. PPP2C overexpression rescued cell invasiveness inhibited by ADGRF4 gene silencing, and PPP2C gene silencing blocked lung cancer cell invasiveness. CONCLUSION: ADGRF4 regulates lung cancer cell invasiveness via PPP2C.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptores Acoplados a Proteínas G/genética , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/mortalidade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Receptores Acoplados a Proteínas G/metabolismo
4.
Biochem Biophys Res Commun ; 532(4): 563-569, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32900487

RESUMO

Environmental toxicants such as dioxins and polycyclic aromatic carbons are risk factors for pancreatitis and pancreatic cancer. These toxicants activate aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, of which activation regulates many downstream biological events, including xenobiotic metabolism, inflammation, and cancer cell growth and transformation. Here, we identified that environmental toxicant-activated AHR increased expression of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in pancreatic cancer cells and pancreatic tissues. The MALAT1 is a long noncoding (lnc) RNA which interacts with Enhancer of Zeste 2 (EZH2), a histone methyltransferase with epigenetic silencer activity, and the MALAT1-EZH2 interaction increased its epigenetic silencing activity. In contrast, AHR antagonist, CH223191 or resveratrol, counteracted the AHR-mediated MALAT1 induction and MALAT1-enahnced EZH2 activity. Collectively, these results revealed a novel pathway of how environmental exposure leads to epigenetic alteration via activation of AHR-MALAT1-EZH2 signaling axis under pancreatic tissue- and cancer cell-context.


Assuntos
Neoplasias Pancreáticas/metabolismo , RNA Longo não Codificante/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Linhagem Celular Tumoral , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Poluentes Ambientais/toxicidade , Humanos , Camundongos Endogâmicos C57BL , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/genética , Dibenzodioxinas Policloradas/toxicidade , RNA Longo não Codificante/biossíntese , Receptores de Hidrocarboneto Arílico/fisiologia , Transdução de Sinais
5.
Anticancer Res ; 40(8): 4529-4535, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727783

RESUMO

BACKGROUND/AIM: Although ginseng seed oil (GSO) appears to have various roles in the body, its anti-cancer effect has not been investigated. Tamoxifen is widely used to treat estrogen receptor-positive (ER+) breast cancer but shows adverse effects with drug resistance. This study investigated the effect of GSO in ER+ breast cancer cell growth. MATERIALS AND METHODS: Cell viability assays, western blots and Annexin V staining were conducted to examine cell viability and apoptosis. The synergistic effect of tamoxifen in combination with GSO or oleic acid (OA) was determined. RESULTS: GSO and OA caused apoptosis of MCF-7 ER+ breast cancer cells and had synergistic effects with tamoxifen in inhibiting tamoxifen-resistant MCF-7 (MCF-7TAMR) ER+ breast cancer cell growth. CONCLUSION: GSO may block ER+ breast cancer recurrence in combination with tamoxifen.


Assuntos
Neoplasias da Mama/metabolismo , Ácido Oleico/farmacologia , Panax/química , Óleos Vegetais/farmacologia , Receptores de Estrogênio/metabolismo , Tamoxifeno/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Células MCF-7 , Óleos Vegetais/química , Sementes/química
6.
Anticancer Res ; 40(1): 213-220, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892569

RESUMO

BACKGROUND/AIM: Kisspeptin produced from the KISS1 gene is secreted from the living cells, binds to endogenous receptor KISS1R (also called G protein-coupled receptor 54, GPR54), and has various functions in normal physiological conditions. Although an anti-metastatic role of kisspeptin in cancer is well known in several cancer types, its role in brain tumors is not yet understood. Herein, we investigated a the role of kisspeptin in glioblastoma cells. MATERIALS AND METHODS: Glioblastoma cells were treated with kisspeptin and subjected to proliferation, migration, and invasion assays. KISS1R dependency was tested by KISS1R silencing with KISS1R siRNAs. RESULTS: Kisspeptin inhibited migratory and invasive abilities of U87-MG, U-251-MG and U373-MG glioblastoma cells with no effect on cell viability. KISS1R gene silencing with KISS1R siRNAs blocked kisspeptin-induced glioblastoma cell invasiveness. Moreover, chemical inhibitors against Gq, PLC or PKC blocked kisspeptin-induced glioblastoma cell invasiveness. CONCLUSION: Kisspeptin induces glioblastoma cell invasiveness via the KISS1R-Gq-PLC-PKC signaling pathway.


Assuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Kisspeptinas/metabolismo , Proteína Quinase C/metabolismo , Transdução de Sinais , Fosfolipases Tipo C/metabolismo , Linhagem Celular Tumoral , Ativação Enzimática , Humanos , Invasividade Neoplásica , Metástase Neoplásica
7.
Planta Med ; 85(16): 1242-1252, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31597167

RESUMO

Numerous chemically synthesized compounds are widely used in oral hygiene products. However, due to their potential risk, there is a need to improve the safety and quality of dental care by seeking alternative control agents such as those naturally found in plant materials. Here we assessed antibacterial potentials of extracts from 100 species of Korean native plants against Streptococcus mutans on cariogenesis. Among those, extracts from five plants (Arctii Fructus, Caryopteris incana, Aralia continentalis, Symplocarpus renifolius, and Lamium amplexicaule) showed a growth inhibition of S. mutans. The five extracts were further individually evaluated for their minimal inhibitory concentration and minimal bactericidal concentration. Interestingly, a synergistic antibacterial activity was observed with the combination of sodium fluoride and the plant extracts. To determine the anti-biofilm activity of plant extracts, S. mutans was treated with increasing concentrations of the extracts in the range from 1250 to 3750 µg/mL. When S. mutans was grown in the defined biofilm medium containing the individual extracts of 47 species, the biofilm amount markedly decreased compared to that of a negative control. Notably, the extract of S. renifolius significantly downregulated the gtf and spaP genes for synthesis of glucan and adhesive proteins in S. mutans, and L. amplexicaule decreased the expression of gtfD gene. Therefore, these results demonstrate that the five plant extracts modulate survival and pathogenesis of S. mutans by growth inhibition and downregulation of the gene(s) implicated in biofilm formation.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Produtos Biológicos/farmacologia , Streptococcus mutans/efeitos dos fármacos , Antibacterianos/química , Produtos Biológicos/química , República da Coreia , Streptococcus mutans/crescimento & desenvolvimento
8.
Anticancer Res ; 38(10): 5791-5798, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30275201

RESUMO

BACKGROUND/AIM: The aim of the present study was to investigate the mechanism through which kisspeptin inhibits colorectal cancer metastasis. MATERIALS AND METHODS: Colorectal cancer cells were treated with kisspeptin and then subjected to assays for cell viability, migration, invasion and anchorage-independent growth. Kisspeptin receptor (KISS1R) requirement was examined by siRNA-based gene silencing followed by western blot and invasion assays. Kisspeptin regulation of PKR and PP2A was examined by treating cells with inhibitors for PKR or PP2A. RESULTS: Kisspeptin inhibited colorectal cancer cell invasiveness without affecting cell proliferation. Kisspeptin required activation of KISS1R and resulted in activation of PKR and PP2A. PKR inhibitor blocked kisspeptin-induced PP2A phosphorylation, while PP2A inhibitor failed to block kisspeptin-induced PKR phosphorylation. CONCLUSION: Kisspeptin-mediated activation of PKR-PP2A inhibited colorectal cancer cell invasiveness.


Assuntos
Neoplasias Colorretais/prevenção & controle , Kisspeptinas/metabolismo , Proteína Fosfatase 2/metabolismo , eIF-2 Quinase/metabolismo , Apoptose , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Kisspeptinas/genética , Invasividade Neoplásica , Fosforilação , Proteína Fosfatase 2/genética , Células Tumorais Cultivadas , eIF-2 Quinase/genética
9.
Mol Med Rep ; 17(2): 2665-2672, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29207134

RESUMO

Chemotherapy frequently causes anorexia in cancer patients, which has been associated with poor disease prognosis. Several therapeutic strategies for the treatment of chemotherapy­induced anorexia are available; however, their adverse effects limit their clinical use. Herbal medicines have a long history of use for the treatment of various diseases, including cancer, and recent research has demonstrated their safety and efficacy. In the present study, combinations of herbal medicines were designed based on traditional Korean medicine, and their effects were investigated on chemotherapy­induced anorexia. Herbal mixtures were extracted, composed of Atractylodes japonica, Angelica gigas, Astragalus membranaceus, Lonicera japonica Thunb., Taraxacum platycarpum H. Dahlstedt and Prunella vulgaris var. asiatica (Nakai) Hara. The mixtures were termed LCBP­Anocure­16001­3 (LA16001, LA16002, LA16003). A cisplatin­induced anorexic mouse model was used to evaluate the putative effects of the extracts on chemotherapy­induced anorexia. Treatment with LA16001 was revealed to prevent body weight loss, and all three extracts were demonstrated to improve food intake. When the molecular mechanisms underlying the orexigenic effects of LA16001 were investigated, altered expression levels of ghrelin, leptin and interleukin­6 were revealed. Furthermore, LA16001 was reported to induce phosphorylation of Janus kinase 1 and signal transducer and activator of transcription 3. In addition, LA16001 administration increased the number of white blood cells and neutrophils. These results suggested that the herbal formula LA16001 may be able to prevent chemotherapy­induced anorexia and may have potential as a novel therapeutic strategy for the adjuvant treatment of patients with cancer.


Assuntos
Anorexia/etiologia , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Extratos Vegetais/farmacologia , Animais , Anorexia/tratamento farmacológico , Anorexia/metabolismo , Apetite/efeitos dos fármacos , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Medicina Herbária , Hormônios/metabolismo , Humanos , Janus Quinase 1/metabolismo , Masculino , Camundongos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Int J Mol Med ; 41(1): 373-380, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115450

RESUMO

Tumor necrosis factor­α­mediated (TNF­α) epithelial­mesenchymal transition (EMT) is associated with distant metastasis in patients with colorectal cancer with poor prognosis. Although traditional herbal medicines have long been used to treat colorectal cancer, the incidence and mortality in patients with colorectal cancer has continued to increase. Danggui­Sayuk­Ga­Osuyu­Saenggang­Tang (DSGOST) has long been used for treatment of chills, while few studies have reported its anticancer effect. This study aimed to demonstrate the inhibitory effect of DSGOST on TNF­α­mediated invasion and migration of colorectal cancer HCT116 cell lines. MTT was used to measure cell viability. Wound healing and Τranswell invasion assay were used to detect migration and invasion of cells, respectively. The intracellular localization of proteins of interest was assessed by immunocytochemistry. Western blotting was performed to determine the expression level of various proteins. A non­toxic dose of DSGOST (50 µg/ml) on HCT116 cells was determined by MTT assay. Furthermore, DSGOST prevented the TNF­α­induced invasive phenotype in HCT116 cells. DSGOST inhibition of the invasive phenotype was also associated with increased expression of EMT markers. Furthermore, DSGOST treatment blocked TNF­α­induced migration and invasion of HCT116 cells. In addition, DSGOST treatment inhibited TNF­α­mediated nuclear translocation of Snail. DSGOST treatment also downregulated TNF­α­induced phosphorylation of AKT and glycogen synthase kinase­3ß. Therefore, the findings of the current study suggest that DSGOST exhibits anti­migration and anti­invasion effects in TNF­α­treated HCT116 human colorectal cells.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Fator de Necrose Tumoral alfa/genética , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Medicamentos de Ervas Chinesas/química , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/genética , Células HCT116 , Humanos , Invasividade Neoplásica/genética , Proteínas Proto-Oncogênicas c-akt/genética , Fator de Necrose Tumoral alfa/administração & dosagem
11.
Oncol Lett ; 14(4): 4845-4852, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29085490

RESUMO

Canonical WNT signaling promotes breast cancer progression. Although APC downregulated 1 (APCDD1) may inhibit canonical WNT signaling, its role in breast cancer remains to be fully understood. The present study demonstrated that APCDD1 suppressed in vitro breast cancer growth and metastasis by inhibiting canonical WNT signaling. The present study demonstrated that APCDD1 expression was negatively associated with breast cancer cell invasion, which was consistent with previous studies that indicated that APCDD1 expression was decreased in invasive ductal carcinoma compared with that in ductal carcinoma in situ. Furthermore, APCDD1 expression was negatively associated with nuclear ß-catenin expression and transcription factor/lymphoid enhancer binding factor 1 transcriptional activity in the present study. Silencing APCDD1 in non-invasive breast cancer cells using lentiviral APCDD1 short hairpin RNAs enhanced migration and invasion, which may be mediated by canonical WNT signaling, whereas the overexpression of human influenza hemagglutinin-tagged APCDD1 in invasive breast cancer cells repressed these properties. Therefore, the present study suggested that APCDD1 regulated breast cancer progression by targeting canonical WNT signaling and modulating breast cancer cell invasion.

12.
Oncotarget ; 8(51): 88386-88400, 2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-29179443

RESUMO

Drug markets revisits herbal medicines, as historical usages address their therapeutic efficacies with less adverse effects. Moreover, herbal medicines save both cost and time in development. SH003, a modified version of traditional herbal medicine extracted from Astragalus membranaceus (Am), Angelica gigas (Ag), and Trichosanthes Kirilowii Maximowicz (Tk) with 1:1:1 ratio (w/w) has been revealed to inhibit tumor growth and metastasis on highly metastatic breast cancer cells, both in vivo and in vitro with no toxicity. Meanwhile, autophagy is imperative for maintenance cellular homeostasis, thereby playing critical roles in cancer progression. Inhibition of autophagy by pharmacological agents induces apoptotic cell death in cancer cells, resulting in cancer treatment. In this study, we demonstrate that SH003-induced autophagy via inhibiting STAT3 and mTOR results in an induction of lysosomal p62/SQSTM1 accumulation-mediated reactive oxygen species (ROS) generation and attenuates tumor growth. SH003 induced autophagosome and autolysosome formation by inhibiting activation of STAT3- and mTOR-mediated signaling pathways. However, SH003 blocked autophagy-mediated p62/SQSTM1 degradation through reducing of lysosomal proteases, Cathepsins, resulting in accumulation of p62/SQSTM1 in the lysosome. The accumulation of p62/SQSTM1 caused the increase of ROS, which resulted in the induction of apoptotic cell death. Therefore, we conclude that SH003 suppresses breast cancer growth by inducing autophagy. In addition, SH003-induced p62/SQSTM1 could function as an important mediator for ROS generation-dependent cell death suggesting that SH003 may be useful for treating breast cancer.

13.
Sci Rep ; 7(1): 10662, 2017 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-28878246

RESUMO

The aryl hydrocarbon receptor (AHR) plays crucial roles in inflammation, metabolic disorder, and cancer. However, the molecular mechanisms regulating AHR expression remain unknown. Here, we found that an orphan nuclear NR2E3 maintains AHR expression, and forms an active transcriptional complex with transcription factor Sp1 and coactivator GRIP1 in MCF-7 human breast and HepG2 liver cancer cell lines. NR2E3 loss promotes the recruitment of LSD1, a histone demethylase of histone 3 lysine 4 di-methylation (H3K4me2), to the AHR gene promoter region, resulting in repression of AHR expression. AHR expression and responsiveness along with H3K4me2 were significantly reduced in the livers of Nr2e3rd7 (Rd7) mice that express low NR2E3 relative to the livers of wild-type mice. SP2509, an LSD1 inhibitor, fully restored AHR expression and H3K4me2 levels in Rd7 mice. Lastly, we demonstrated that both AHR and NR2E3 are significantly associated with good clinical outcomes in liver cancer. Together, our results reveal a novel link between NR2E3, AHR, and liver cancer via LSD1-mediated H3K4me2 histone modification in liver cancer development.


Assuntos
Reprogramação Celular/genética , Regulação Neoplásica da Expressão Gênica , Histona Desmetilases/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Receptores Nucleares Órfãos/deficiência , Receptores de Hidrocarboneto Arílico/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Biologia Computacional/métodos , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Modelos Biológicos , Prognóstico , Receptores de Hidrocarboneto Arílico/metabolismo
14.
Mol Med Rep ; 16(5): 7585-7590, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28944853

RESUMO

Kisspeptin is a protein encoded by the KISS1 gene, which has been reported to suppress the metastatic capabilities of various types of cancer cells, through the activation of its G­protein coupled receptor GPR54. However, the molecular mechanisms underlying the involvement of kisspeptin­mediated signaling in the inhibition of cancer cell migration and invasion have yet to be elucidated. The present in vitro cell proliferation, migration and invasion assays and in vivo experimental metastasis studies demonstrated that kisspeptin­induced eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) activation suppressed the metastatic capabilities of several types of cancer cells. Kisspeptin was revealed to inhibit the migratory and invasive abilities of highly metastatic breast SK­BR­3, prostatic PC­3 and colorectal adenocarcinoma LoVo human cancer cell lines, whereas its inhibitory effects were abolished following the silencing of EIF2AK2 expression using RNA interference. Similarly, kisspeptin failed to inhibit the migration and invasion of mouse embryonic fibroblasts following the deletion of the EIF2AK2 gene. Furthermore, kisspeptin was demonstrated to activate Ras homolog gene family member A (RhoA)­dependent signaling, and to phosphorylate EIF2AK2 via RhoA­mediated pathways in various cancer cells. In addition, results obtained from nude mice bearing LoVo­derived xenograft tumors revealed that kisspeptin inhibited tumor growth through an EIF2AK2­dependent mechanism, and an in vivo metastasis assay identified kisspeptin­activated EIF2AK2 signaling as critical for the suppression of distant metastasis. The present study concluded that kisspeptin represses cancer metastasis via EIF2AK2 signaling, thus clarifying the role of kisspeptin signaling in complicated cancer metastasis signaling network. Therefore, kisspeptin treatment may be a choice for blocking metastases.


Assuntos
Kisspeptinas/metabolismo , Neoplasias/patologia , eIF-2 Quinase/metabolismo , Animais , Linhagem Celular , Movimento Celular , Proliferação de Células , Humanos , Camundongos , Camundongos Nus , Metástase Neoplásica , Neoplasias/metabolismo , Fosforilação , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transplante Heterólogo , eIF-2 Quinase/antagonistas & inibidores , eIF-2 Quinase/genética , Proteína rhoA de Ligação ao GTP/metabolismo
15.
Oncol Lett ; 14(2): 2511-2516, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28781689

RESUMO

Breast cancer is one of the most common types of cancer in women, and its metastasis increases the risk of mortality. Melatonin, a hormone that regulates the circadian rhythm, has been revealed to inhibit breast cancer growth and metastasis. However, its involvement in highly metastatic triple-negative breast cancer cells is yet to be elucidated. The present study demonstrated that melatonin inhibited the metastatic abilities of triple-negative breast cancer cells and prolonged its inhibitory effect via the expression of kisspeptin (KiSS1), which is a suppressor of metastasis. Melatonin at concentrations ranging from 1 nM to 10 µM did not affect the proliferation of metastatic MDA-MB-231 and HCC-70 triple-negative breast cancer cells. However, melatonin repressed invasiveness in triple-negative breast cancer cells. Additionally, conditional medium from melatonin-treated MDA-MB-231 cells repressed the invasiveness of triple-negative breast cancer cells. Melatonin promoted the production of KiSS1, a metastasis suppressor encoded by the KiSS1 gene. In addition, melatonin increased KiSS1 expression via the expression and transcriptional activation of GATA binding protein 3. Silencing of KiSS1 weakened melatonin inhibition of breast cancer cell invasiveness. Therefore, the present study concluded that melatonin activates KiSS1 production in metastatic breast cancer cells, suggesting that melatonin activation of KiSS1 production may regulate the process of breast cancer metastasis.

16.
Biomed Rep ; 6(6): 681-685, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28584641

RESUMO

Cancer remains a leading cause of mortality worldwide, therefore food products are being investigated for potential prevention or treatment strategies. The ingredient, barley grass extract (Hordeum vulgare L.; Bex) is used to prevent or ameliorate various types of disease. In cancer, Bex has been revealed to inhibit tumor growth. However, its effect on cancer cells is yet to be clearly defined. In the present study, the effect of Bex on cancer cell growth was investigated. Bex inhibited the viabilities of breast and prostate cancer cells according to the results of MTT assays. Accordingly, Bex caused apoptosis, which was confirmed by Annexin V staining and western blot analysis for poly (ADP-ribose) polymerase and caspases. Furthermore, Bex increased the intracellular levels of reactive oxygen species (ROS), and N-acetyl-L-cystein blocked Bex-induced apoptosis. Therefore, the study demonstrated that Bex causes apoptosis of breast and prostate cancer cells by increasing intracellular ROS levels.

17.
Mol Med Rep ; 15(5): 3143-3146, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28350093

RESUMO

The herbal extract Angelica gigas (AG) has been applied as a vasodilating agent for patients suffering from vascular diseases for many years; however, the underlying mechanism has not been fully elucidated. The present study hypothesized that the anti­vasoconstrictive effect of AG may be effective in the treatment of abnormal cold­mediated vasospasms that occur in Raynaud's phenomenon (RP). The effect of AG on the activity of ras homolog gene family member A (RhoA) was investigated in cold­exposed vascular cells. Vascular cells were pretreated to AG, followed by a warm (37˚C) or cold (25˚C) incubation for 30 min and investigated with western blotting, ELISA and confocal microscopy. Cold treatment induced the activation of RhoA in pericytes and vascular endothelial cells, however this was reduced by treatment with AG. Furthermore, AG treatment reduced the endothelin­1 (ET­1)­mediated RhoA activation in pericytes; however, cold­induced ET­1 production by vascular endothelial cells was not affected by treatment with AG. In addition, AG treatment suppressed the formation of stress fibers and focal adhesion complexes, and the cold­induced phosphorylation of focal adhesion kinase, proto­oncogene tyrosine­protein kinase Src and extracellular signal­related kinase. Therefore, AG treatment demonstrated an ability to reduce cold­induced RhoA activation in pericytes and vascular endothelial cells, and attenuated ET­1­mediated RhoA activation in pericytes. In conclusion, the present study indicated that AG may be useful for the treatment of RP.


Assuntos
Angelica/química , Extratos Vegetais/química , Proteína rhoA de Ligação ao GTP/metabolismo , Angelica/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Endotelina-1/análise , Endotelina-1/metabolismo , Ensaio de Imunoadsorção Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Microscopia Confocal , Pericitos/citologia , Pericitos/efeitos dos fármacos , Pericitos/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Temperatura , Vasodilatadores/química , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia , Quinases da Família src/metabolismo
18.
Mol Cell Biochem ; 426(1-2): 1-8, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27854072

RESUMO

Paclitaxel is an anti-cancer drug for treating cancer, but paclitaxel resistance is reported in cancer cells. Multidrug resistance (MDR) is related with the epithelial-to-mesenchymal transition (EMT) mechanism, which plays a key role in cancer metastasis. Moreover, EMT mechanism is connected to tamoxifen resistance in breast cancer cells. Consequently, oncologists are interested in finding new MDR1 inhibitors originating from herbal medicines to have less side-effect. Here, we investigated an inhibition effect of SH003 on MDR1 activity in paclitaxel-resistant MCF-7/PAX breast cancer cells. Our results showed that paclitaxel did not inhibit a proliferation in paclitaxel-resistant MCF-7 breast cancer cells. Paclitaxel-resistant MCF-7 cells showed an increase of MDR1 activity, which was confirmed by measuring an amount of accumulated rhodamine 123 in the cells. Also, qRT-PCR and Western blot assays confirmed that paclitaxel-resistant MCF-7 cells exhibited high MDR1 expression level. Furthermore, paclitaxel-resistant MCF-7 cells showed mesenchymal morphology with alterations of EMT markers, and acquired tamoxifen resistance with a decrease of ERα expression. We also found that a combinatorial treatment of SH003 and paclitaxel in paclitaxel-resistant MCF-7 cells caused apoptosis in synergistic manner, which was due to SH003 inhibition of MDR1 expression. Therefore, SH003 could be a potential agent for overcoming MDR in drug-resistant cancer cells.


Assuntos
Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas de Neoplasias , Paclitaxel/farmacologia , Extratos Vegetais/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo
19.
BMC Complement Altern Med ; 16(1): 507, 2016 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-27927199

RESUMO

BACKGROUND: Herbal medicines have been used in cancer treatment, with many exhibiting favorable side effect and toxicity profiles compared with conventional chemotherapeutic agents. SH003 is a novel extract from Astragalus membranaceus, Angelica gigas, and Trichosanthes Kirilowii Maximowicz combined at a 1:1:1 ratio that impairs the growth of breast cancer cells. This study investigates anti-cancer effects of SH003 in prostate cancer cells. METHODS: SH003 extract in 30% ethanol was used to treat the prostate cancer cell lines DU145, LNCaP, and PC-3. Cell viability was determined by MTT and BrdU incorporation assays. Next, apoptotic cell death was determined by Annexin V and 7-AAD double staining methods. Western blotting was conducted to measure protein expression levels of components of cell death and signaling pathways. Intracellular reactive oxygen species (ROS) levels were measured using H2DCF-DA. Plasmid-mediated ERK2 overexpression in DU145 cells was used to examine the effect of rescuing ERK2 function. Results were analyzed using the Student's t-test and P-values < 0.05 were considered to indicate statistically-significant differences. RESULTS: Our data demonstrate that SH003 induced apoptosis in DU145 prostate cancer cells by inhibiting ERK signaling. SH003 induced apoptosis of prostate cancer cells in dose-dependent manner, which was independent of androgen dependency. SH003 also increased intracellular ROS levels but this is not associated with its pro-apoptotic effects. SH003 inhibited phosphorylation of Ras/Raf1/MEK/ERK/p90RSK in androgen-independent DU145 cells, but not androgen-dependent LNCaP and PC-3 cells. Moreover, ERK2 overexpression rescued SH003-induced apoptosis in DU145 cells. CONCLUSIONS: SH003 induces apoptotic cell death of DU145 prostate cancer cells by inhibiting ERK2-mediated signaling.


Assuntos
Apoptose/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Extratos Vegetais/farmacologia
20.
Mol Med Rep ; 14(5): 4723-4728, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27748811

RESUMO

Danggui-Sayuk-Ga-Osuyu-Senggang-Tang (DSGOST), one of the traditional Chinese medicines, has long been prescribed for patients suffering from Raynaud phenomenon (RP) in Northeast Asian countries, including China, Japan and Korea. Although a previous in vitro study from our laboratory revealed that DSGOST prevents cold (25˚C)­induced RhoA activation and endothelin­1 (ET­1) production in endothelial cells (ECs), the mechanisms by which DSGOST is able to alleviate the symptoms of RP have yet to be fully elucidated. The present study aimed to demonstrate that DSGOST regulates RhoA­mediated pathways in cold­exposed pericytes. In pericytes, DSGOST amplified cold­induced RhoA activation, while markedly reducing ET­1­induced RhoA activation. Additionally, DSGOST­mediated regulation of RhoA was closely associated with Rho­associated, coiled­coil­containing protein kinase 1 (ROCK1)/testis­specific kinase 1 (TESK1)/PDXP, but not with LIM domain kinase 1/2 (LIMK1/2), cofilin and myosin light chain (MLC). Thus, DSGOST activation of RhoA/ROCK1/TESK1/PDXP in cold­exposed pericytes appeared to be crucial for treating vessel contraction. In addition, the DSGOST effect on the RhoA­mediated pathway in cold­induced human umbilical vein endothelial cells or human dermal microvascular endothelial cells was similar to that in ET­1­treated pericytes, but not in cold­induced pericytes. The results of the present study further confirmed that DSGOST inhibits cold­induced contraction of the mouse tail vein in vivo. Furthermore, DSGOST treatment reduced cold­induced expression of the α2c­adrenergic receptor in mouse tail vessels. Therefore, the data in the present study suggest that DSGOST may be useful for the treatment of RP­like disease.


Assuntos
Temperatura Baixa , Medicamentos de Ervas Chinesas/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Endotelina-1/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos , Pericitos/efeitos dos fármacos , Pericitos/metabolismo , Receptores Adrenérgicos alfa 2/metabolismo , Transdução de Sinais/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...