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1.
Biochem Pharmacol ; 150: 191-201, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29454618

RESUMO

Bigelovin, a sesquiterpene lactone, has been demonstrated to induce apoptosis, inhibit inflammation and angiogenesis in vitro, but its potential anti-metastatic activity remains unclear. In the present study, two colon cancer mouse models, orthotopic tumor allografts and experimental metastatic models were utilized to investigate the progression and metastatic spread of colorectal cancer after bigelovin treatments. Results showed that bigelovin (intravenous injection; 0.3-3 mg/kg) significantly suppressed tumor growth and inhibited liver/lung metastasis with modulation of tumor microenvironment (e.g. increased populations of T lymphocytes and macrophages) in orthotopic colon tumor allograft-bearing mice. Furthermore, the inhibitory activities were also validated in the experimental human colon cancer metastatic mouse model. The underlying mechanisms involved in the anti-metastatic effects of bigelovin were then revealed in murine colon tumor cells colon 26-M01 and human colon cancer cells HCT116. Results showed that bigelovin induced cytotoxicity, inhibition of cell proliferation, motility and migration in both cell lines, which were through interfering IL6/STAT3 and cofilin pathways. Alternations of the key molecules including Rock, FAK, RhoA, Rac1/2/3 and N-cadherin, which were detected in bigelovin-treated cancer cells, were also observed in the tumor allografts of bigelovin-treated mice. These findings strongly indicated that bigelovin has potential to be developed as anti-tumor and anti-metastatic agent for colorectal cancer.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Inibidores do Crescimento/administração & dosagem , Interleucina-6/metabolismo , Lactonas/administração & dosagem , Fator de Transcrição STAT3/metabolismo , Sesquiterpenos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Animais , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Neoplasias Colorretais/metabolismo , Células HCT116 , Humanos , Injeções Intravenosas , Interleucina-6/antagonistas & inibidores , Masculino , Camundongos , Camundongos Nus , Fator de Transcrição STAT3/antagonistas & inibidores , Transdução de Sinais/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
2.
Zhongguo Zhong Yao Za Zhi ; 39(9): 1620-4, 2014 May.
Artigo em Chinês | MEDLINE | ID: mdl-25095372

RESUMO

To investigate monoterpenes and sesquiterpenes of the stems and leaves of Clausena excavata, an AcOEt fraction of the methanol extract was subjected on column chromatographies including silica gel and RP-18, as well as preparative HPLC. The structures of compounds isolated were identified on the basis of spectroscopic data as excamonoterpene (1), (6R, 9S)-9, 10-dihydroxy-4-megastigmen-3-one (2), (3R, 6R, 7E) -3-hydroxy-4, 7-megastigmadien-9-one (3), (3S) -3-hydroxy-7, 8-dihydro-beta-ionone (4), (3S, 5R, 6S) -3-hydroxy-5,6-epoxy-beta-ionone (5), (6R, 9R) -9-hydroxy-4-megastigmen-3-one (6), (3S, SR) -dihydroxy-6, 7-megstigmadien-9-one(7), (-)-loliolide(8), caryolane-1, 9alpha-diol(9) and 2, 6-dihydroxyhumula-3 (12), 7 (13), 9(E)-triene (10), were isolated from the stems and leaves of C. excavata. Compound 1 is a new monoterpene, named as excamonoterpene. Compounds 2-10 were isolated from this plant for the first time.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Clausena/química , Monoterpenos/análise , Sesquiterpenos/análise , Espectroscopia de Ressonância Magnética , Metanol/química , Estrutura Molecular , Monoterpenos/química , Folhas de Planta/química , Caules de Planta/química , Sesquiterpenos/química , Espectrometria de Massas por Ionização por Electrospray
3.
Yao Xue Xue Bao ; 49(12): 1689-93, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25920198

RESUMO

A new phenethanol, (2'R)-4-(2', 3'-dihydroxy-3'-methyl-butanoxy)-phenethanol (1), along with other eleven known benzene derivatives (2-12) were isolated from the roots, stems and leaves of Clausena excavata (Rutaceae). Compounds 3 and 4 are new natural products, and compounds 5-8, 10-12 were isolated from C. excavata for the first time. Their structures were elucidated on the basis of MS, 1D and 2D NMR spectroscopic analyses including HSQC, COSY and HMBC experiments. 1 was tested for its cytotoxicities against A549, HeLa and BGC-823 cancer cell lines, and antimicrobial activities against Candida albicans and Staphylococcus aureus. The results showed that 1 did not exhibit cytotoxic and antimicrobial activities.


Assuntos
Derivados de Benzeno/química , Clausena/química , Candida albicans/efeitos dos fármacos , Linhagem Celular Tumoral , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Folhas de Planta/química , Raízes de Plantas/química , Caules de Planta/química , Staphylococcus aureus/efeitos dos fármacos
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