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1.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33805784

RESUMEN

Hepatocellular carcinoma (HCC) frequently shows early invasion into blood vessels as well as intrahepatic metastasis. Innovations of novel small-molecule agents to block HCC invasion and subsequent metastasis are urgently needed. Moscatilin is a bibenzyl derivative extracted from the stems of a traditional Chinese medicine, orchid Dendrobium loddigesii. Although moscatilin has been reported to suppress tumor angiogenesis and growth, the anti-metastatic property of moscatilin has not been elucidated. The present results revealed that moscatilin inhibited metastatic behavior of HCC cells without cytotoxic fashion in highly invasive human HCC cell lines. Furthermore, moscatilin significantly suppressed the activity of urokinase plasminogen activator (uPA), but not matrix metalloproteinase (MMP)-2 and MMP-9. Interestingly, moscatilin-suppressed uPA activity was through down-regulation the protein level of uPA, and did not impair the uPA receptor and uPA inhibitory molecule (PAI-1) expressions. Meanwhile, the mRNA expression of uPA was inhibited via moscatilin in a concentration-dependent manner. In addition, the expression of phosphorylated Akt, rather than ERK1/2, was inhibited by moscatilin treatment. The expression of phosphor-IκBα, and -p65, as well as κB-luciferase activity were also repressed after moscatilin treatment. Transfection of constitutively active Akt (Myr-Akt) obviously restored the moscatilin-inhibited the activation of NF-κB and uPA, and cancer invasion in HCC cells. Taken together, these results suggest that moscatilin impedes HCC invasion and uPA expression through the Akt/NF-κB signaling pathway. Moscatilin might serve as a potential anti-metastatic agent against the disease progression of human HCC.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Compuestos de Bencilo/farmacología , Movimiento Celular/efectos de los fármacos , FN-kappa B/genética , Proteínas Proto-Oncogénicas c-akt/genética , Activador de Plasminógeno de Tipo Uroquinasa/genética , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Embrión de Pollo , Membrana Corioalantoides/irrigación sanguínea , Membrana Corioalantoides/efectos de los fármacos , Factor 4E Eucariótico de Iniciación/genética , Factor 4E Eucariótico de Iniciación/metabolismo , Regulación Neoplásica de la Expresión Génica , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/prevención & control , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/antagonistas & inhibidores , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo
2.
Phytomedicine ; 64: 152911, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31454653

RESUMEN

Background Garcimultiflorone K is a novel polyprenylated polycyclic acylphloroglucinol isolated from the stems of Garcinia multiflora that exhibits promising anti-angiogenic activity in human endothelial progenitor cells (EPCs). Purpose This study sought to determine the underlying anti-angiogenic mechanisms and pharmacological properties of garcimultiflorone K. Methods We examined the anti-angiogenic effects of garcimultiflorone K and its mechanisms of action using in vitro EPC models and in vivo zebrafish embryos. Results EPCs proliferation, migration, differentiation and capillary-like tube formation were effectively and concentration-dependently inhibited by garcimultiflorone K without any signs of cytotoxicity. Our investigations revealed that garcimultiflorone K suppressed EPCs angiogenesis through Akt, mTOR, p70S6K, and eNOS signaling cascades. Notably, garcimultiflorone K dose-dependently impeded angiogenesis in zebrafish embryos. Conclusion Our data demonstrate the anti-angiogneic effects of garcimultiflorone K in both in vitro and in vivo models. Garcimultiflorone K appears to have potential in the treatment of angiogenesis-related diseases.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Garcinia/química , Neovascularización Patológica/tratamiento farmacológico , Floroglucinol/farmacología , Transducción de Señal/efectos de los fármacos , Inhibidores de la Angiogénesis/química , Animales , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Progenitoras Endoteliales/efectos de los fármacos , Humanos , Óxido Nítrico Sintasa de Tipo III/metabolismo , Floroglucinol/química , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Pez Cebra
3.
Nano Lett ; 17(9): 5614-5619, 2017 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-28746807

RESUMEN

Phase transitions in correlated materials can be manipulated at the nanoscale to yield emergent functional properties, promising new paradigms for nanoelectronics and nanophotonics. Vanadium dioxide (VO2), an archetypal correlated material, exhibits a metal-insulator transition (MIT) above room temperature. At the thicknesses required for heterostructure applications, such as an optical modulator discussed here, the strain state of VO2 largely determines the MIT dynamics critical to the device performance. We develop an approach to control the MIT dynamics in epitaxial VO2 films by employing an intermediate template layer with large lattice mismatch to relieve the interfacial lattice constraints, contrary to conventional thin film epitaxy that favors lattice match between the substrate and the growing film. A combination of phase-field simulation, in situ real-time nanoscale imaging, and electrical measurements reveals robust undisturbed MIT dynamics even at preexisting structural domain boundaries and significantly sharpened MIT in the templated VO2 films. Utilizing the sharp MIT, we demonstrate a fast, electrically switchable optical waveguide. This study offers unconventional design principles for heteroepitaxial correlated materials, as well as novel insight into their nanoscale phase transitions.

4.
J Bone Miner Res ; 32(1): 34-45, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27465842

RESUMEN

Angiogenesis is the formation of new capillaries from preexisting vasculature. The perpetuation of angiogenesis plays a critical role in the pathogenesis of various disease states including rheumatoid arthritis (RA). Cysteine-rich 61 (Cyr61 or CCN1) is an important proinflammatory cytokine in RA. Here, we investigated the role of CCN1 in angiogenesis associated with vascular endothelial growth factor (VEGF) production and osteoblasts. We found higher expression of CCN1 and VEGF in synovial fluid from RA patients compared with healthy controls. CCN1 induced VEGF expression in osteoblasts and increased endothelial progenitor cells (EPCs) angiogenesis by inhibiting miR-126 via the protein kinase C-alpha (PKC-α) signaling pathway. CCN1 knockdown inhibited angiogenesis in both in vitro and in vivo models. Inhibition of CCN1 expression with lentiviral vectors expressing short hairpin RNA (shRNA) ameliorated articular swelling, cartilage erosion, and angiogenesis in the ankle joint of mice with collagen-induced arthritis (CIA). Our study is the first to describe how CCN1 promotes VEGF expression in osteoblasts and increased EPCs angiogenesis in RA disease. CCN1 may serve as a potential target for RA treatment. © 2016 American Society for Bone and Mineral Research.


Asunto(s)
Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Proteína 61 Rica en Cisteína/metabolismo , Células Progenitoras Endoteliales/metabolismo , MicroARNs/metabolismo , Neovascularización Fisiológica , Osteoblastos/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Adulto , Animales , Artritis Experimental/metabolismo , Artritis Experimental/patología , Pollos , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones Endogámicos C57BL , MicroARNs/genética , Persona de Mediana Edad , Proteína Quinasa C-alfa/metabolismo , Transducción de Señal , Líquido Sinovial/metabolismo
5.
BMC Complement Altern Med ; 15: 445, 2015 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-26694191

RESUMEN

BACKGROUND: Melanoma is an aggressive skin cancer and a predominant cause of skin cancer-related deaths. A previous study has demonstrated the ability of butein to inhibit tumor proliferation and invasion. However, the anti-metastatic mechanisms and in vivo effects of butein have not been fully elucidated. METHODS: MTT cell viability assays were used to evaluate the antitumor effects of butein in vitro. Cytotoxic effects of butein were measured by lactate dehydrogenase assay. Anti-migratory effects of butein were evaluated by two-dimensional scratch and transwell migration assays. Signaling transduction and VEGF-releasing assays were measured by Western blotting and ELISA. We also conducted an experimental analysis of the metastatic potential of tumor cells injected into the tail vein of C57BL/6 mice. RESULTS: We first demonstrated the effect of butein on cell viability at non-cytotoxic concentrations (1, 3, and 10 µM). In vitro, butein was found to inhibit the migration of B16F10 cells in a concentration-dependent manner using transwell and scratch assays. Butein had a dose-dependent effect on focal adhesion kinase, Akt, and ERK phosphorylation in B16F10 cells. Butein efficiently inhibited the mTOR/p70S6K translational inhibition machinery and decreased the production of VEGF in B16F10 cells. Furthermore, the in vivo antitumor effects of butein were demonstrated using a pulmonary metastasis model. CONCLUSION: The results of the present study indicate the potential utility of butein in the treatment of melanoma.


Asunto(s)
Chalconas/administración & dosificación , Melanoma Experimental/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Melanoma Experimental/fisiopatología , Ratones , Ratones Endogámicos C57BL , Metástasis de la Neoplasia , Transducción de Señal/efectos de los fármacos , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/fisiopatología , Factor A de Crecimiento Endotelial Vascular/genética
6.
J Agric Food Chem ; 62(37): 9109-17, 2014 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-25137351

RESUMEN

Tumor metastasis is the major obstacle for cancer treatment. Previous studies have shown that butein exhibits antiangiogenesis property and anticancer effects in different kinds of human cancer cells. However, the effects of butein on metastasis and energy metabolism of cancer cells are mostly unknown. This study showed that butein significantly inhibited invasion of cancer cells without acting in a cytotoxic fashion. It was further demonstrated that butien dramatically suppressed cancer metastasis by an in vivo CAM-intravasation model. Additionally, butein concentration-dependently repressed the expression and activity of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA). The study indicated that butein may repress MMP-9 and uPA proteolytic activities and subsequently inhibit cancer metastasis via Akt/mTOR/p70S6K translational machinery. Moreover, butein may partly suppress cancer metastasis by down-regulating ATP synthesis via both oxidative and glycolytic metabolism. The results suggest that butein is a potential antimetastatic agent worthy of further development for cancer treatment.


Asunto(s)
Antineoplásicos/farmacología , Chalconas/farmacología , Metabolismo Energético/efectos de los fármacos , Metástasis de la Neoplasia/prevención & control , Adenosina Trifosfato/biosíntesis , Carcinoma Hepatocelular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Glucólisis/efectos de los fármacos , Humanos , Neoplasias Hepáticas , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Invasividad Neoplásica/prevención & control , Fosforilación Oxidativa/efectos de los fármacos , Activador de Plasminógeno de Tipo Uroquinasa/antagonistas & inhibidores
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