Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Molecules ; 25(9)2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32349276

RESUMO

Pancreatic cancer (PC) is one of the most severe cancers, and its incidence and mortality rates have steadily increased in the past decade. In this study, we demonstrate the effect of Angelica gigas Nakai extract on pancreatic ductal adenocarcinoma cells. We prepared A. gigas Nakai ethanol extract (AGE) using roots of A. gigas Nakai and detected its active compound decursin from AGE by ultra-performance liquid chromatography analysis. AGE and decursin significantly decreased viability and colony formation of PANC-1 and MIA PaCa-2 cells. AGE and decursin induced G0/G1 phase arrest through downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). Caspase-3-dependent apoptosis of PANC-1 cells was promoted by AGE and decursin. Additionally, nontoxic concentrations of AGE and decursin treatment could suppress matrix metalloproteinase (MMP)-2 and MMP-9 expression and activity by inhibiting p38 phosphorylation. Taken together, this study demonstrates that AGE and decursin have potential properties to be considered in PC treatment.

2.
Phytomedicine ; 68: 153147, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32028184

RESUMO

BACKGROUND: Gomisin A (G.A), a lignan compound extracted from the fruits of Schisandra chinensis, is known to exert anti-tumor effects on hepatocarcinoma and colorectal cancer cells. Suppression of proliferation and metastatic abilities of cancer cells are some effective cancer treatment methods. PURPOSE: The objective of this study is to investigate the effects of G.A on metastatic melanoma, and the mechanism by which it affects metastatic melanoma. STUDY DESIGN: The anti-proliferative and anti-metastatic effects of G.A were observed in in vitro and in vivo. METHODS: WST assay and flow cytometry were conducted to investigate the effect of G.A on proliferation, cell cycle arrest, and apoptosis in metastatic melanoma cell lines. Migration and invasion abilities of G.A-treated melanoma cells were observed by wound healing and invasion assays. RESULTS: G.A (25-100 µM) decreased the viability of melanoma cells by inducing cell cycle arrest and apoptosis. These anti-proliferative effects of G.A were found to be mediated by AMPK, ERK, and JNK activation. G.A (5-20 µM) decreased the migration and invasion of melanoma cells by suppressing epithelial-mesenchymal transition (EMT). Consequently, G.A (2-50 mg/kg) inhibited lung metastasis by suppressing EMT and inducing cell cycle arrest and apoptosis in melanoma cells. CONCLUSION: These results conclude that G.A has the potential to reduce metastatic melanoma through its anti-proliferative and anti-metastatic effects.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ciclo-Octanos/farmacologia , Dioxóis/farmacologia , Lignanas/farmacologia , Melanoma/tratamento farmacológico , Melanoma/patologia , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , MAP Quinase Quinase 4/metabolismo , Melanoma/metabolismo , Camundongos Endogâmicos C57BL , Ensaios Antitumorais Modelo de Xenoenxerto
3.
J Hazard Mater ; 379: 120830, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31271937

RESUMO

Highly efficient catalytic reaction systems are developed to rapidly and selectively oxidize 2-chloroethyl ethyl sulfide (CEES). In the systems, precursors containing bromide(s) and nitrate anions are chosen for the development of cyclic catalytic loop and the effect of acids on the selective oxidation of CEES are investigated by the addition of several homogeneous acid catalysts. The experimental results reveal that addition of acid results in a higher concentration of tribromide, which is reported as a key component for the observed activity in the catalytic solution. As a consequence, a dramatic improvement in catalytic activity is observed, especially when the molar amount of acid is controlled to be more than twice the initial concentration of tribromide. For the efficient design of a catalytic system, heterogeneous acid catalysts possessing different ratios of Brønsted to Lewis acid sites are also considered. Compared to reaction systems catalysed by homogeneous acids, similar reaction behaviour is observed for the reaction with Amerlyst-15, while those with other heterogeneous catalysts, containing Lewis or mixed acid sites in their structure, exhibits an adverse effect of selective sulfoxidation, mainly due to the adsorption of anions onto Lewis sites and consequential deconstruction of the catalytic loop.

4.
Phytomedicine ; 62: 152952, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31132754

RESUMO

BACKGROUND: Although rubrofusarin-6-ß-gentiobioside (RFG), which is a component of Cassiae tora seed, could likely regulate hyperlipidemia, its anti-obesity effect and related mechanism have not been elucidated. PURPOSE: The aim of this study was to examine whether RFG can ameliorate obesity and the mechanism of lipid accumulation regulated by RFG. STUDY DESIGN: In in vitro experiments, we confirmed the anti-adipogenic effect of RFG using 3T3-L1 cells and human adipose mesenchymal stem cells (hAMSCs). To confirm the anti-obesity effect, High-Fat Diet (HFD)-induced obese mice were selected as a model. METHODS: We investigated anti-adipogenic effects of RFG using MTS assay, Oil Red O Staining, real-time RT-PCR, western blot analysis, and immunofluorescence staining. The anti-obesity effect of RFG was confirmed in HFD-induced mice model using hematoxylin and eosin staining and serum analysis. RESULTS: RFG inhibited lipid accumulation in 3T3-L1 cells and hAMSCs by reducing expression of mammalian targets of rapamycin (mTOR), peroxisome proliferator-activated receptor (PPAR)γ, and CCAAT-enhancer binding protein (C/EBP)α. RFG phosphorylated AMP-activated protein kinase (AMPK) in a liver kinase B (LKB) 1-independent manner. Moreover, the anti-adipogenic effect of RFG was blocked by AMPK inhibitor. These results suggest that RFG inhibits lipid accumulation via AMPK signaling. Furthermore, RFG reduced the body weight, size of epididymal white adipose tissue (eWAT), and fatty liver in the mice. RFG also suppressed levels of adipogenic factors PPARγ, C/EBPα, FAS, LPL, and aP2) by activating AMPK in the eWAT and liver. CONCLUSION: RFG can ameliorate obesity, and thus, could be used as a therapeutic agent for treating obesity.


Assuntos
Fármacos Antiobesidade/farmacologia , Cromonas/farmacologia , Glucosídeos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adipogenia/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Serina-Treonina Quinases TOR/metabolismo
5.
J Ginseng Res ; 43(1): 68-76, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30662295

RESUMO

Background: In colorectal cancer (CRC), 40-60% of patients develop metastasis. The epithelial-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of CRC. The aim of this study was to investigate the effect of Korean Red Ginseng extract (RGE) on colorectal metastasis through inhibition of EMT and the metastatic abilities of CRC cells. Methods: To investigate the effect of RGE on the metastatic phenotypes of CRC cells, CT26 and HT29 cells were evaluated by using an adhesion assay, a wound-healing assay, an invasion assay, zymography, and real-time reverse transcription-polymerase chain reaction. Western-blot analysis was conducted to elucidate the molecular mechanisms of RGE, which showed an inhibitory effect on the transforming growth factor-ß1 (TGF-ß1)-induced EMT in HT29 cells. Additionally, the antimetastatic effect of RGE was evaluated in a mouse model of lung metastasis injected with CT26 cells. Results: RGE decreased the adhesion and migration ability of the CT26 cells and TGF-ß1-treated HT29 cells. The invasion ability was also reduced by RGE treatment through the inhibition of matrix metalloproteinase-9 expression and activity. Moreover, RGE suppressed the TGF-ß1-induced EMT via TGF-ß1/Smad-signaling-mediated Snail/E-cadherin expression in HT29 cells and lung tissue in CT26 tumor-bearing mice. Conclusion: Our results demonstrated that RGE inhibited colorectal lung metastasis through a reduction in metastatic phenotypes, such as migration, invasion, and the EMT of CRC cells.

6.
J Hazard Mater ; 365: 511-518, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30466049

RESUMO

A new metal-free catalytic reaction system is developed to selectively oxidize 2-chloroethyl ethyl sulfide (CEES), a surrogate of sulfur mustard. The combination of two catalytic precursors, tribromide and nitrate, allows a rapid sulfoxidation of CEES even at ambient conditions. The kinetic behaviours at various reaction conditions are investigated to identify the most probable reaction pathways of the development of catalytic loop and the overall reaction steps of CEES sulfoxidation. The mechanistic study demonstrates that the catalytic loop does not require an addition of mineral acid or water, which is common in most other reaction systems. Incomplete catalytic systems with one precursor are also examined to uncover the complex network of sulfoxidation in the catalytic reaction system. The results reveal that the complex between CEES and bromine is a reactive intermediate, bromosulfonium, which can be further catalysed and converted into sulfoxide by nitrate. Based on the proposed reaction mechanism, a predictive kinetic model fully describing most reaction behaviours is developed.

7.
Oncol Rep ; 41(1): 202-212, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30365120

RESUMO

Galla Rhois is a commonly used medicine in East Asia for the treatment of several diseases. However, the effects of Galla Rhois on the metastasis of colorectal cancer (CRC) and the underlying molecular mechanisms have not been studied. We investigated the anti­metastatic properties of Galla Rhois water extract (GRWE) on metastatic CRC cells. The effect of GRWE on the viability of colon 26 (CT26) cells was evaluated using WST­8 assay. Annexin V assay and western blot analysis were performed to elucidate the underlying molecular mechanisms involved in apoptosis. GRWE suppressed viability of CT26 cells by inducing apoptosis through the cleavage of caspase­3 and PARP, downregulation of caspase­8, caspase­9, Bcl­2 and Bcl­xL, and upregulation of Bax. Metastatic phenotypes such as epithelial­mesenchymal transition (EMT), migration, and invasion of CRC cells were investigated by real­time reverse transcription polymerase chain reaction, wound healing assay, and matrigel invasion assay, respectively. Non­cytotoxic concentrations of GRWE inhibited EMT in CRC cells by regulating the expression of EMT markers. GRWE attenuated cell migration and invasion through the inhibition of matrix metalloproteinase (MMP)­2 and MMP­9 activity. Moreover, GRWE suppressed colorectal lung metastasis in vivo, suggestive of its potential application for the treatment of colorectal metastasis.


Assuntos
Adenilato Quinase/metabolismo , Produtos Biológicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Animais , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Nutrients ; 12(1)2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31887988

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the diseases with high prevalence and mortality worldwide. In particular, metastatic CRC shows low probability of surgery and lacks proper treatment. In this study, we conducted experiments to investigate the inhibitory effect of betulin against metastatic CRC and related mechanisms. METHODS: Water-soluble tetrazolium assay was used to determine the effect of betulin on metastatic CRC cell viability. Flow cytometry and TUNEL assay were performed to confirm whether betulin can induce apoptosis, autophagy, and cell cycle arrest. A lung metastasis mouse model was employed to estimate the anti-metastatic effect of betulin. RESULTS: betulin decreased viability of metastatic CRC cells, including CT26, HCT116, and SW620 cell lines. Through PI3K/Akt/mTOR inactivation, betulin induced AMPK-mediated G0/G1 phase arrest and autophagy of CT26 and HCT116 cells. In addition, betulin occurred caspase-dependent apoptosis via the mitogen-activated protein kinase signaling pathway in metastatic CRC cells. Moreover, orally administered betulin significantly inhibited metastasis of CT26 cells to the lung. CONCLUSION: Our results demonstrate the anti-metastatic effect and therapeutic potential of betulin in metastatic CRC treatment.

9.
Front Pharmacol ; 9: 986, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30210348

RESUMO

Gomisin A (G.A) is a dietary lignan compound from Schisandra chinensis. In this study, the effect of G.A on the proliferation and metastasis of colorectal cancer (CRC) cells was investigated using several CRC cell lines and a lung metastasis mouse model. Both oral and intraperitoneal administration of G.A (50 mg/kg) inhibited lung metastasis of CT26 cells. Various concentrations of G.A were incubated with CRC cell lines and their viability was determined using a cell counting kit-8 assay. G.A significantly decreased the viability of various CRC cell lines, whereas it did not change the proliferation of normal colon cells. G.A induced G0/G1 phase arrest and apoptosis of CT26 and HT29 cells by regulating cyclin D1/cyclin-dependent kinase 4 (CDK4) expression and apoptotic proteins such as caspases and B-cell lymphoma-2 (Bcl-2) family proteins, respectively. G.A-induced apoptosis was mediated by AMPK/p38 activation in CRC cells. A non-cytotoxic concentration of G.A inhibited epithelial-mesenchymal transition of CRC cells by modulating E-cadherin and N-cadherin expression levels. Moreover, the migration and invasion of CRC cells were reduced by G.A treatment. Especially, G.A decreased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities. G.A ameliorated lung metastasis of CRC cells by decreasing cell survival and metastatic abilities of CRC cells. Thus, G.A might be a potential novel therapeutic agent for metastatic CRC.

10.
J Ethnopharmacol ; 220: 177-187, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29601980

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The pharmacological effect derived from herb-herb interaction is important to constitute the prescription especially in traditional oriental medicine. The relationship of two medicinal herbs is called "couplet medicinals" which is used in pair for the purpose of enhancing the therapeutic effect, reducing the toxic effect or the adverse effect. The "Eighteen Incompatible Medicaments" constitute one of the contents in the incompatibility of traditional oriental drugs in a prescription. Among the "Eighteen Incompatible Medicaments", the roots and rhizomes of Veratrum nigrum (VN), is incompatible with the roots and rhizomes of Panax ginseng (PG). However, definite evidences of adverse effect by these combinations has yet to be reported. MATERIALS AND METHODS: The aim of the present study was to investigate the effects of ethanol extracts of PG, VN, and their combination (P + V) on the metastatic ability of colorectal cancer (CRC) cells using WST assay, flow cytometry, western blot analysis, real-time RT-PCR, immunofluorescence, migration assay, invasion assay, zymography, and an in vivo experiment with a lung-metastasis mouse model. RESULTS: The PG extract decreased cell proliferation by inducing cell cycle arrest and apoptosis of CRC cells. In addition, PG inhibited metastatic abilities of CRC cells including Epithelial-Mesenchymal Transition, migration, and invasion. Additionally, the PG extract suppressed lung metastasis of the CRC cells in the mouse model. However, the P + V extract exhibited weaker anti-proliferative and anti-metastatic effects than PG alone. CONCLUSION: Based on these results, the P + V couplet medicinal attenuates the anti-metastatic effects of PG, both in vitro and in vivo.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Panax/química , Extratos Vegetais/farmacologia , Veratrum/química , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/administração & dosagem , Raízes de Plantas , Rizoma
11.
Front Pharmacol ; 9: 68, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29459827

RESUMO

Rosmarinic acid (RA) has been used as an anti-inflammatory, anti-diabetic, and anti-cancer agent. Although RA has also been shown to exert an anti-metastatic effect, the mechanism of this effect has not been reported to be associated with AMP-activated protein kinase (AMPK). The aim of this study was to elucidate whether RA could inhibit the metastatic properties of colorectal cancer (CRC) cells via the phosphorylation of AMPK. RA inhibited the proliferation of CRC cells through the induction of cell cycle arrest and apoptosis. In several metastatic phenotypes of CRC cells, RA regulated epithelial-mesenchymal transition (EMT) through the upregulation of an epithelial marker, E-cadherin, and the downregulation of the mesenchymal markers, N-cadherin, snail, twist, vimentin, and slug. Invasion and migration of CRC cells were inhibited and expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were decreased by RA treatment. Adhesion and adhesion molecules such as ICAM-1 and integrin ß1 expressions were also reduced by RA treatment. In particular, the effects of RA on EMT and MMPs expressions were due to the activation of AMPK. Moreover, RA inhibited lung metastasis of CRC cells by activating AMPK in mouse model. Collectively, these results proved that RA could be potential therapeutic agent against metastasis of CRC.

12.
Am J Chin Med ; 45(6): 1309-1325, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28830210

RESUMO

Although Arctii Fructus (AF) has been shown to have various pharmacological effects, there have been no studies concerning the inhibitory effects of AF on the metastatic properties of colorectal cancer (CRC). The aim of this study was to investigate whether AF could suppress CRC progression by inhibiting cell growth, epithelial-mesenchymal transition (EMT), migration, and the invasion ability of CRC cells. AF decreased proliferation of CRC cells by inducing cell cycle arrest and apoptosis via extrinsic and intrinsic apoptotic pathways. Regarding metastatic properties, AF inhibited EMT by increasing the expression of the epithelial marker, E-cadherin, and decreasing the expression of the mesenchymal marker, N-cadherin, in CT26 cells. Moreover, AF decreased the migration and invasion of CT26 cells by inhibiting matrix metalloproteinase-2 (MMP-2) and MMP-9 activity. We confirmed that the decreased invasion ability and MMP-9 activity by AF treatment involved AMP-activated protein kinase (AMPK) activation. Collectively, this study demonstrates that AF inhibits the proliferation and metastatic properties of CRC cells.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Arctium/química , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Frutas/química , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Extratos Vegetais/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caderinas/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Extratos Vegetais/isolamento & purificação
13.
Am J Chin Med ; 45(5): 1047-1060, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28659027

RESUMO

Eclipta prostrata (EP) and its compounds are known to have several pharmacological effects including anti-inflammatory effects. In the present study, we demonstrated that EP improves the dextran sulfate sodium (DSS)-induced colitis symptoms such as body weight loss, colon length shortening and disease activity index. In DSS-induced colitis tissue, EP controls the protein expressions of cyclooxygenase-2 (COX-2) and hypoxia inducible factor-1[Formula: see text] (HIF-1[Formula: see text]). In addition, the release of prostaglandin E2 and vascular endothelial growth factor-A were significantly reduced by EP administration. EP also inhibited COX-2 and HIF-1[Formula: see text] expressions in the tumor necrosis factor-[Formula: see text] stimulated HT-29 cells. These inhibitory effects of EP occurred by reducing the phosphorylation of I[Formula: see text]B and the translocation of the nuclear factor-[Formula: see text]B (NF-[Formula: see text]B). Additionally, we found through HPLC analysis that wedelolactone, which is an inhibitor of NF-[Formula: see text]B transcription, was contained in water extract of EP. These results indicate that EP can improve colitis symptoms through the modulation of immune function in intestinal epithelial cells and suggests that EP has the potential therapeutic effect to intestinal inflammation.


Assuntos
Anti-Inflamatórios , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Eclipta/química , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Mediadores da Inflamação/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Doença Aguda , Animais , Células Cultivadas , Colite/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Feminino , Células HT29 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo
14.
PLoS One ; 12(5): e0176937, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28481901

RESUMO

ß-Lapachone is a natural quinone compound from Lapacho trees, which has various pharmacological effects such as anti-bacterial, anti-fungal, anti-viral, and anti-inflammatory activities. However, the effect of ß-lapachone on metastasis of melanoma cells is unclear. In this study, ß-lapachone reduced cell viability of metastatic melanoma cancer cell lines B16F10 and B16BL6 through induction of apoptosis via the mitogen-activated protein kinase (MAPK) pathway. Additionally, flow cytometry results showed that ß-lapachone increased DNA content in the G0/G1 phase of the cell cycle. Analysis of the mechanisms of these events indicated that ß-lapachone regulated the expression of Bcl-2, Bcl-xL, and Bax, resulting in the activation of caspase-3, -8, -9, and poly-ADP-ribose polymerase (PARP). Moreover, the ß-lapachone-administered group showed significantly decreased lung metastasis in the experimental mouse model. In conclusion, our study demonstrates the inhibitory effect of ß-lapachone on lung metastasis of melanoma cells and provides a new insight into the role of ß-lapachone as a potential antitumor agent.


Assuntos
Neoplasias Pulmonares/prevenção & controle , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma/patologia , Naftoquinonas/farmacologia , Metástase Neoplásica/prevenção & controle , Animais , Feminino , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos C57BL
15.
J Ginseng Res ; 41(2): 134-143, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28413317

RESUMO

BACKGROUND: The prevalence of allergic inflammatory diseases such as atopic dermatitis (AD), asthma, and allergic rhinitis worldwide has increased and complete recovery is difficult. Korean Red Ginseng, which is the heat-processed root of Panax ginseng Meyer, is widely and frequently used as a traditional medicine in East Asia. In this study, we investigated whether Korean Red Ginseng water extract (RGE) regulates the expression of proinflammatory cytokines and chemokines via the mitogen-activated protein kinases (MAPKs)/nuclear factor kappa B (NF-κB) pathway in allergic inflammation. METHODS: Compound 48/80-induced anaphylactic shock and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced AD-like skin lesion mice models were used to investigate the antiallergic effects of RGE. Human keratinocytes (HaCaT cells) and human mast cells (HMC-1) were also used to clarify the effects of RGE on the expression of proinflammatory cytokines and chemokines. RESULTS: Anaphylactic shock and DNFB-induced AD-like skin lesions were attenuated by RGE administration through reduction of serum immunoglobulin E (IgE) and interleukin (IL)-6 levels in mouse models. RGE also reduced the production of proinflammatory cytokines including IL-1ß, IL-6, and IL-8, and expression of chemokines such as IL-8, thymus and activation-regulated chemokine (TARC), and macrophage-derived chemokine (MDC) in HaCaT cells. Additionally, RGE decreased the release of tumor necrosis factor-α (TNF-α), IL-1ß, IL-6, and IL-8 as well as expressions of chemokines including macrophage inflammatory protein (MIP)-1α, MIP-1ß, regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, and IL-8 in HMC-1 cells. Furthermore, our data demonstrated that these inhibitory effects occurred through blockage of the MAPK and NF-κB pathway. CONCLUSION: RGE may be a useful therapeutic agent for the treatment of allergic inflammatory diseases such as AD-like dermatitis.

16.
Integr Cancer Ther ; 16(4): 585-596, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-27923905

RESUMO

BACKGROUND: ß-Lapachone is a quinone-containing compound found in red lapacho ( Tabebuia impetiginosa, syn. T avellanedae) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of ß-lapachone and the underlying mechanisms using colon cancer cells. METHODS: This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38). A WST assay, annexin V assay, cell cycle analysis, wound healing assay, invasion assay, western blot analysis, and real-time reverse transcription-polymerase chain reaction were performed to examine the effects of ß-lapachone on metastatic phenotypes and molecular mechanisms. The effect of ß-lapachone on lung metastasis was assessed in a mouse experimental metastasis model. RESULTS: We found that the inhibition of proliferation of the colon cancer cell lines by ß-lapachone was due to the induction of apoptosis and cell cycle arrest. ß-Lapachone induced the apoptosis of CT26 cells through caspase-3, -8, and -9 activation; poly(ADP-ribose) polymerase cleavage; and downregulation of the Bcl-2 family in a dose- and time-dependent manner. In addition, a low concentration of ß-lapachone decreased the cell migration and invasion by decreasing the expression of matrix metalloproteinases-2 and -9, and increased the expression of tissue inhibitors of metalloproteinases-1 and -2. Moreover, ß-lapachone treatment regulated the expression of epithelial-mesenchymal transition markers such as E- and N-cadherin, vimentin, ß-catenin, and Snail in CT26 cells. In the mouse experimental metastasis model, ß-lapachone significantly inhibited the lung metastasis of CT26 cells. CONCLUSIONS: Our results demonstrated the inhibitory effect of ß-lapachone on colorectal lung metastasis. This compound may be useful for developing therapeutic agents to treat metastatic cancer.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Naftoquinonas/farmacologia , Animais , Biomarcadores Tumorais/metabolismo , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Regulação para Baixo/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
17.
Food Funct ; 7(12): 5025-5033, 2016 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-27882370

RESUMO

Arctii Fructus is traditionally used in oriental pharmacies as an anti-inflammatory medicine. Although several studies have shown its anti-inflammatory effects, there have been no reports on its use in obesity related studies. In this study, the anti-obesity effect of Arctii Fructus was investigated in high-fat diet (HFD)-induced obese mice, and the effect was confirmed in white and primary cultured brown adipocytes. Arctii Fructus inhibited weight gain and reduced the mass of white adipose tissue in HFD-induced obese mice. Serum levels of triglyceride and LDL-cholesterol were reduced, and HDL-cholesterol was increased in the Arctii Fructus treated group. In 3T3-L1 cells, a water extract (WAF) and 70% EtOH extract (EtAF) of Arctii Fructus significantly inhibited adipogenesis and suppressed the expression of proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha. In particular, EtAF activated the phosphorylation of AMP-activated protein kinase. On the other hand, uncoupling protein 1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, known as brown adipocytes specific genes, were increased in primary cultured brown adipocytes by WAF and EtAF. This study shows that Arctii Fructus prevents the development of obesity through the inhibition of white adipocyte differentiation and activation of brown adipocyte differentiation which suggests that Arctii Fructus could be an effective therapeutic for treating or preventing obesity.


Assuntos
Adipócitos/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Arctium/química , Gorduras na Dieta/efeitos adversos , Extratos Vegetais/farmacologia , Células 3T3-L1 , Animais , Fármacos Antiobesidade/química , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Gorduras na Dieta/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama/genética , PPAR gama/metabolismo , Extratos Vegetais/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
18.
Phytomedicine ; 23(13): 1680-1690, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27823633

RESUMO

BACKGROUND: Quercetin is a major dietary flavonoid found in a various fruits, vegetables, and grains. Although the inhibitory effects of quercetin have previously been observed in several types of cancer cells, the anti-metastatic effect of quercetin on colorectal metastasis has not been determined. PURPOSE: This study investigated whether quercetin exhibits inhibitory effect on colorectal lung metastasis. STUDY DESIGN: The effects of quercetin on cell viability, mitogen-activated protein kinases (MAPKs) activation, migration, invasion, epithelial-mesenchymal transition (EMT) and lung metastasis were investigated. METHODS: We investigated the effect of quercetin on metastatic colon cancer cells using WST assay, Annexin V assay, real-time RT-PCR, western blot analysis and gelatin zymography. The anti-metastatic effect of quercetin in vivo was confirmed in a colorectal lung metastasis model. RESULTS: Quercetin inhibited the cell viability of colon 26 (CT26) and colon 38 (MC38) cells and induced apoptosis through the MAPKs pathway in CT26 cells. Expression of EMT markers, such as E-, N-cadherin, ß-catenin, and snail, were regulated by non-toxic concentrations of quercetin. Moreover, the migration and invasion abilities of CT26 cells were inhibited by quercetin through expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) regulation. Quercetin markedly decreased lung metastasis of CT26 cells in an experimental in vivo metastasis model. CONCLUSION: In conclusion, this study demonstrates for the first time that quercetin can inhibit the survival and metastatic ability of CT26 cells, and it can subsequently suppress colorectal lung metastasis in the mouse model. These results indicate that quercetin may be a potent therapeutic agent for the treatment of metastatic colorectal cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/patologia , Neoplasias Pulmonares/tratamento farmacológico , Quercetina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HT29/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Metaloproteinases da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo
19.
Molecules ; 21(9)2016 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-27618887

RESUMO

Arctigenin (ARC) has been shown to have an anti-cancer effect in various cell types and tissues. However, there have been no studies concerning metastatic colorectal cancer (CRC). In this study, we investigated the anti-metastatic properties of ARC on colorectal metastasis and present a potential candidate drug. ARC induced cell cycle arrest and apoptosis in CT26 cells through the intrinsic apoptotic pathway via MAPKs signaling. In several metastatic phenotypes, ARC controlled epithelial-mesenchymal transition (EMT) through increasing the expression of epithelial marker E-cadherin and decreasing the expressions of mesenchymal markers; N-cadherin, vimentin, ß-catenin, and Snail. Moreover, ARC inhibited migration and invasion through reducing of matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. In an experimental metastasis model, ARC significantly inhibited lung metastasis of CT26 cells. Taken together, our study demonstrates the inhibitory effects of ARC on colorectal metastasis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Furanos/farmacologia , Lignanas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica
20.
Biosci Biotechnol Biochem ; 80(12): 2391-2400, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27494072

RESUMO

Acanthopanax henryi (Oliv.) Harms has been used in the treatment of arthritis, rheumatism, and abdominal pain. This study evaluated whether natural compounds isolated from the leaves of A. henryi (Oliv.) Harms could inhibit adipocyte differentiation by regulating transcriptional factors such as peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). AMP-activated protein kinase (AMPK) activity was also evaluated. Among the several compounds isolated from the leaves of A. henryi (Oliv.) Harms, Glycoside St-C1 and Glycoside St-E2 significantly decreased lipid accumulation and the expressions of PPARγ and C/EBPα. Glycoside St-C1 and Glycoside St-E2 were found to activate AMPK when they regulated PPARγ and C/EBPα. Results confirmed that Glycoside St-C1 and Glycoside St-E2 isolated from the leaves of A. henryi (Oliv.) Harms can inhibit adipogenesis through the AMPK-PPARγ-C/EBPα mechanism. Thus, this study suggests that Glycoside St-C1 and Glycoside St-E2 have a therapeutic effect due to activation of the AMPKα.


Assuntos
Adipogenia/efeitos dos fármacos , Eleutherococcus/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Folhas de Planta/química , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , PPAR gama/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA