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1.
Phytother Res ; 26(6): 932-7, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22162124

RESUMO

Although matrine, a primary active component of dried Sophora flavescens root (ku shen), is known to induce apoptosis in a variety of tumor cells in vitro, the molecular mechanism of such apoptosis remains elusive. This analysis of the cell cycle and apoptosis in matrine-treated human gallbladder carcinoma cells (GBC-SD) showed that matrine can indeed inhibit cell proliferation and induce G1 cell cycle arrest and apoptosis in a dose- and time-dependent manner. An additional western blot analysis of matrine-treated cells also showed caspase-3 and Bcl-2 activation, as well as cyclinE down-regulation. Overall, the results indicate that matrine perturbs gallbladder cancer cell progression during the G1 phase by down-regulating cyclinE and induces apoptosis by decreasing the expression of the antiapoptotic protein Bcl-2 and increasing expression of the proapoptotic protein Bax.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Proliferação de Células/efeitos dos fármacos , Quinolizinas/farmacologia , Western Blotting , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclina E/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ativação Enzimática , Pontos de Checagem da Fase G1 do Ciclo Celular , Neoplasias da Vesícula Biliar/patologia , Humanos , Sophora/química , Fatores de Tempo , Proteína X Associada a bcl-2/metabolismo , Matrinas
2.
J Ethnopharmacol ; 137(3): 1373-80, 2011 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-21855619

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: A traditional Chinese medicine Scutellaria baicalensis is prescribed for the treatment of a variety of inflammatory diseases and tumors in clinic in China. However, the detailed mechanism of anti-metastasis effect of wogonin, a main active ingredient of Scutellaria baicalensis, remains elusive. AIM OF THE STUDY: The present study was designed to investigate the action and mechanism of wogonin on the mobility and invasion of human gallbladder carcinoma GBC-SD cells. MATERIALS AND METHODS: Viability, apoptosis, mRNA and protein expression of tumor cells were analyzed by MTT, Annexin V staining, real-time PCR and Western blot, respectively. The migration and invasion assay was used to evaluate the anti-metastasis effect of wogonin. Knockdown of maspin was performed by specific small interference RNA. RESULTS: Wogonin at the dose of 1-10 µM, which did not induce apoptosis, significantly inhibited the mobility and invasion activity of human gallbladder carcinoma GBC-SD cells. In addition, the expressions of matrix metalloproteinase (MMP)-2, MMP-9 and phosphorylated extracellular regulated protein kinase 1/2 (ERK1/2) but not phosphorylated Akt were dramatically suppressed by wogonin in a concentration-dependent manner. Furthermore, the metastasis suppressor maspin was confirmed as the downstream target of wogonin. Both maspin mRNA and protein were upregulated by wogonin. Interestingly, the knockdown of maspin resulted in almost completely blocking of wogonin-induced inhibition of MMP-2, MMP-9 and phosphorylated ERK1/2 as well as the mobility and invasion activity of GBC-SD cells. CONCLUSIONS: These findings suggest that wogonin inhibits cell mobility and invasion by upregulating the metastasis suppressor maspin. Together, these data provide novel insights into the chemoprotective effect of wogonin, a main active ingredient of Chinese medicine Scutellaria baicalensis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma/secundário , Movimento Celular/efeitos dos fármacos , Flavanonas/farmacologia , Neoplasias da Vesícula Biliar/patologia , Extratos Vegetais/farmacologia , Serpinas/metabolismo , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Carcinoma/genética , Carcinoma/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Flavanonas/isolamento & purificação , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/metabolismo , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Invasividade Neoplásica , Fosforilação , Extratos Vegetais/química , Plantas Medicinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Scutellaria baicalensis/química , Serpinas/genética , Fatores de Tempo , Regulação para Cima
3.
Cancer Lett ; 298(2): 222-30, 2010 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-20674153

RESUMO

In this study, the anticancer effect of icariin, a natural flavonol glycoside, against human hepatoma SMMC-7721 cells and the underlying mechanisms were investigated. Icariin triggered the mitochondrial/caspase apoptotic pathway indicated by enhanced Bax-to-Bcl-2 ratio, loss of mitochondrial membrane potential, cytochrome c release, and caspase cascade. Moreover, icariin induced a sustained activation of the phosphorylation of c-Jun N-terminal kinase (JNK) but not p38 and ERK1/2, and SP600125 (an inhibitor of JNK) almost reversed icariin-induced apoptosis in SMMC-7721 cells. In addition, icariin provoked the generation of reactive oxygen species (ROS) in SMMC-7721 cells, while the antioxidant N-acetyl cysteine almost completely blocked icariin-induced JNK activation and apoptosis. Taken together, these findings suggest that icariin induces apoptosis through a ROS/JNK-dependent mitochondrial pathway.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/prevenção & controle , Flavonoides/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Hepáticas Experimentais/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Plant Mol Biol ; 61(6): 845-61, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16927200

RESUMO

Elucidating the regulatory mechanisms of plant organ formation is an important component of plant developmental biology and will be useful for crop improvement applications. Plant organ formation, or organogenesis, occurs when a group of primordial cells differentiates into an organ, through a well-orchestrated series of events, with a given shape, structure and function. Research over the past two decades has elucidated the molecular mechanisms of organ identity and dorsalventral axis determinations. However, little is known about the molecular mechanisms underlying the successive processes. To develop an effective approach for studying organ formation at the molecular level, we generated organ-specific gene expression profiles (GEPs) reflecting early development in rice stamen. In this study, we demonstrated that the GEPs are highly correlated with early stamen development, suggesting that this analysis is useful for dissecting stamen development regulation. Based on the molecular and morphological correlation, we found that over 26 genes, that were preferentially up-regulated during early stamen development, may participate in stamen development regulation. In addition, we found that differentially expressed genes during early stamen development are clustered into two clades, suggesting that stamen development may comprise of two distinct phases of pattern formation and cellular differentiation. Moreover, the organ-specific quantitative changes in gene expression levels may play a critical role for regulating plant organ formation.


Assuntos
Flores/genética , Perfilação da Expressão Gênica , Oryza/genética , Análise por Conglomerados , Etiquetas de Sequências Expressas , Flores/crescimento & desenvolvimento , Flores/ultraestrutura , Regulação da Expressão Gênica no Desenvolvimento/genética , Regulação da Expressão Gênica de Plantas/genética , Hibridização In Situ , Microscopia Eletrônica de Varredura , Análise de Sequência com Séries de Oligonucleotídeos , Oryza/crescimento & desenvolvimento , Pólen/genética , Pólen/crescimento & desenvolvimento , Pólen/ultraestrutura , Fatores de Tempo
5.
J Exp Bot ; 54(389): 1995-6, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12815033

RESUMO

A novel SET-domain-containing gene OsSET1 was isolated from rice (Oryza sativa L.). Its deduced protein consists of 895 amino acids. OsSET1 has a high degree of structure similarity to other SET-domain-containing genes such as CLF in higher plants and E(z) in animals. RT-PCR showed that the gene expresses throughout the entire plant. A transient expression assay in onion epidermis revealed that the OsSET1 protein is localized in nuclei. Over-expression of the SET domain of OsSET1 in Arabidopsis resulted in altered shoot development at seedling stages.


Assuntos
Genes de Plantas/genética , Oryza/genética , Proteínas de Plantas/química , Proteínas de Plantas/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Arabidopsis/genética , Núcleo Celular/metabolismo , Clonagem Molecular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Dados de Sequência Molecular , Cebolas/citologia , Cebolas/genética , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Estrutura Terciária de Proteína , Plântula/genética , Plântula/crescimento & desenvolvimento
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