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Métodos Terapéuticos y Terapias MTCI
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1.
Phytother Res ; 34(8): 2032-2043, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32144852

RESUMEN

Esophageal cancer (EC) is one of the leading causes to cancer death in the worldwide and major population of EC is esophageal squamous cell carcinoma (ESCC). Still, ESCC-targeted therapy has not been covered yet. In the present study we have identified that Licochalcone B (Lico B) inhibited the ESCC growth by directly blocking the Janus kinase (JAK) 2 activity and its downstream signaling pathway. Lico B suppressed KYSE450 and KYSE510 ESCC cell growth, arrested cell cycle at G2/M phase and induced apoptosis. Direct target of Lico B was identified by kinase assay and verified with in vitro and ex vivo binding. Computational docking model predicted for Lico B interaction to ATP-binding pocket of JAK2. Furthermore, treatment of JAK2 clinical medicine AZD1480 to ESCC cells showed similar tendency with Lico B. Thus, JAK2 downstream signaling proteins phosphorylation of STAT3 at Y705 and S727 as well as STAT3 target protein Mcl-1 expression was decreased with treatment of Lico B. Our results suggest that Lico B inhibits ESCC cell growth, arrests cell cycle and induces apoptosis, revealing the underlying mechanism involved in JAK2/STAT3 signaling pathways after Lico B treatment. It might provide potential role of Lico B in the treatment of ESCC.


Asunto(s)
Chalconas/uso terapéutico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Janus Quinasa 2/antagonistas & inhibidores , Apoptosis , Línea Celular Tumoral , Chalconas/farmacología , Carcinoma de Células Escamosas de Esófago/patología , Humanos
2.
Mol Plant Microbe Interact ; 33(5): 721-723, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32003591

RESUMEN

Micromonospora terminaliae sp. nov., type strain TMS7T, is a gram-positive nonmotile aerobic actinobacterium that was recently isolated from a surface-sterilized stem of the medicinal plant Terminalia mucronata. This strain was described as a novel species in the Micromonospora genus. To elucidate the application potential of this species, its genome was completely sequenced, using the PacBio SMRT cell platform, and was compared with selected complete genome sequences of other Micromonospora species. Genomic analysis revealed that the genome of TMS7T consists of one circular DNA chromosome of 6,717,200 bp with a GC content of 73.35% and one plasmid of 24,912 bp with a GC content of 65.39%. The entire genome contains 6,311 predicted coding genes, 57 transfer RNAs, and nine ribosomal RNA genes. The genome contains a type III polyketide biosynthesis gene cluster, which encodes enzymes that catalyze the production of alkyl-O-dihydrogeranyl-methoxyhydroquinone. This information combined with the previous report that this strain can grow well on pH 10 medium with 4% NaCl (wt/vol) indicates that this strain may have potential biocontrol applications for economic plants cultivated on alkaline soil.


Asunto(s)
Genoma Bacteriano , Micromonospora/genética , Terminalia/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Hibridación de Ácido Nucleico , Filogenia , Plantas Medicinales/microbiología , Análisis de Secuencia de ADN
3.
Phytomedicine ; 61: 152813, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31035049

RESUMEN

BACKGROUND: Colorectal cancer is one of the most common causes of cancer death worldwide. Unfortunately, chemotherapies are limited due to many complications and development of resistance and recurrence. The T-lymphokine-activated killer cell-originated protein kinase (TOPK) is highly expressed and activated in colon cancer, and plays an important role in inflammation, proliferation, and survival of cancer cells. Therefore, suppressing TOPK activity and its downstream signaling cascades is considered to be a rational therapeutic/preventive strategy against colon cancers. PURPOSE: 3-Deoxysappanchalcone (3-DSC), a component of Caesalpinia sappan L., is a natural oriental medicine. In this study, we investigated the effects of 3-DSC on colon cancer cell growth and elucidated its underlying molecular mechanism of targeting TOPK. STUDY DESIGN AND METHODS: To evaluate the effects of 3-DSC against colon cancer, we performed cell proliferation assays, propidium iodide- and annexin V-staining analyses and Western blotting. Targeting TOPK by 3-DSC was identified by a kinase-binding assay and computational docking models. RESULTS: 3-DSC inhibited the kinase activity of TOPK, but not mitogen-activated protein kinase (MEK). The direct binding of 3-DSC with TOPK was explored using a computational docking model and binding assay in vitro and ex vivo. 3-DSC inhibited colon cancer cell proliferation and anchorage-independent cell growth, and induced G2/M cell cycle arrest and apoptosis. Treatment of colon cancer cells with 3-DSC induced expression of protein that are involved in cell cycle (cyclin B1) and apoptosis (cleaved-PARP, cleaved-caspase-3, and cleaved-caspase-7), and suppressed protein expressions of extracellular signal-regulated kinase (ERK)-1/2, ribosomal S6 kinase (RSK), and c-Jun, which are regulated by the upstream kinase, TOPK. CONCLUSION: 3-DSC suppresses colon cancer cell growth by directly targeting the TOPK- mediated signaling pathway.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Chalconas/farmacología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Chalconas/química , Neoplasias del Colon/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Quinasas de Proteína Quinasa Activadas por Mitógenos/química , Simulación del Acoplamiento Molecular , Terapia Molecular Dirigida/métodos , Inhibidores de Proteínas Quinasas/farmacología , Transducción de Señal/efectos de los fármacos
4.
Mol Cancer Ther ; 17(7): 1540-1553, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29695636

RESUMEN

Overexpression or activation of AKT is very well known to control cell growth, survival, and gene expression in solid tumors. Oridonin, an inflammatory medical and diterpenoid compound isolated from Rabdosia rubescens, has exhibited various pharmacologic and physiologic properties, including antitumor, antibacterial, and anti-inflammatory effects. In this study, we demonstrated that oridonin is an inhibitor of AKT and suppresses proliferation of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo The role of AKT in ESCC was studied using immuno-histochemical analysis of a tumor microarray, the effect of AKT knockdown on cell growth, and treatment of cells with MK-2206, an AKT inhibitor. Oridonin blocked AKT kinase activity and interacted with the ATP-binding pocket of AKT. It inhibited growth of KYSE70, KYSE410, and KYSE450 esophageal cancer cells in a time- and concentration-dependent manner. Oridonin induced arrest of cells in the G2-M cell-cycle phase, stimulated apoptosis, and increased expression of apoptotic biomarkers, including cleaved PARP, caspase-3, caspase-7, and Bims in ESCC cell lines. Mechanistically, we found that oridonin diminished the phosphorylation and activation of AKT signaling. Furthermore, a combination of oridonin and 5-fluorouracil or cisplatin (clinical chemotherapeutic agents) enhanced the inhibition of ESCC cell growth. The effects of oridonin were verified in patient-derived xenograft tumors expressing high levels of AKT. In summary, our results indicate that oridonin acts as an AKT inhibitor to suppress the growth of ESCC by attenuating AKT signaling. Mol Cancer Ther; 17(7); 1540-53. ©2018 AACR.


Asunto(s)
Diterpenos de Tipo Kaurano/farmacología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Isodon/química , Proteína Oncogénica v-akt/genética , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Diterpenos de Tipo Kaurano/química , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Ratones , Proteína Oncogénica v-akt/antagonistas & inhibidores , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
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