RESUMO
We investigated the effect of Ecklonia cava (E. cava)-derived dieckol on movement behavior and the expression of migration-related genes in MCF-7 human breast cancer cell. Phlorotannins (e.g., dieckol, 6,6'-biecko, and 2,7â³-phloroglucinol-6,6'-bieckol) were purified from E. cava by using centrifugal partition chromatography. Among the phlorotannins, we found that dieckol inhibited breast cancer cell the most and was selected for further study. Radius™-well was used to assess cell migration, and dieckol (1-100 µM) was found to suppress breast cancer cell movement. Metastasis-related gene expressions were evaluated by RT-PCR and Western blot analysis. In addition, dieckol inhibited the expression of migration-related genes such as matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF). On the other hand, it stimulated the expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These results suggest that dieckol exerts anti-breast cancer activity via the regulation of the expressions of metastasis-related genes, and this is the first report on the anti-breast cancer effect of dieckol.
Assuntos
Antineoplásicos/isolamento & purificação , Benzofuranos/isolamento & purificação , Neoplasias da Mama/tratamento farmacológico , Descoberta de Drogas , Phaeophyceae/química , Alga Marinha/química , Taninos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzofuranos/química , Benzofuranos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dioxanos/química , Dioxanos/isolamento & purificação , Dioxanos/farmacologia , Dioxinas/química , Dioxinas/isolamento & purificação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Metaloproteinase 9 da Matriz/química , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Neoplasias/agonistas , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Oceano Pacífico , Phaeophyceae/crescimento & desenvolvimento , Floroglucinol/análogos & derivados , Floroglucinol/química , Floroglucinol/isolamento & purificação , Floroglucinol/farmacologia , República da Coreia , Alga Marinha/crescimento & desenvolvimento , Taninos/química , Taninos/farmacologia , Inibidor Tecidual de Metaloproteinase-1/agonistas , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/agonistas , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Selaginella tamariscina is a traditional medicinal plant for treatment of some advanced cancers in the Orient. However, the effect of S. tamariscina on metastasis of osteosarcoma and the underlying mechanism remain unclear. We tested the hypothesis that S. tamariscina suppresses cellular motility, invasion and migration and also investigated its signaling pathways. This study demonstrates that S. tamariscina, at a range of concentrations (from 0 to 50 µg/mL), concentration-dependently inhibited the migration/invasion capacities of three osteosarcoma cell lines without cytotoxic effects. Zymographic and western blot analyses revealed that S. tamariscina inhibited the matrix metalloproteinase (MMP)-2 and MMP-9 enzyme activity, as well as protein expression. Western blot analysis also showed that S. tamariscina inhibits phosphorylation of p38 and Akt. Furthermore, SB203580 (p38 inhibitor) and LY294002 (PI3K inhibitor) showed the similar effects as S. tamariscina in U2OS cells. In conclusion, S. tamariscina possesses an antimetastatic activity in osteosarcoma cells by down-regulating MMP-2 and MMP-9 secretions and increasing TIMP-1 and TIMP-2 expressions through p38 and Akt-dependent pathways. S. tamariscina may be a powerful candidate to develop a preventive agent for osteosarcoma metastasis.
Assuntos
Inibidores da Angiogênese/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Metaloproteinases de Matriz/farmacologia , Osteossarcoma/tratamento farmacológico , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Selaginellaceae/química , Inibidores da Angiogênese/isolamento & purificação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Etnofarmacologia , Humanos , Metaloproteinase 2 da Matriz/química , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/química , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/isolamento & purificação , Medicina Tradicional do Leste Asiático , Proteínas de Neoplasias/agonistas , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Osteossarcoma/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Taiwan , Inibidor Tecidual de Metaloproteinase-1/agonistas , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/agonistas , Inibidor Tecidual de Metaloproteinase-2/metabolismoRESUMO
Rhizoma Paridis saponins (RPS) have been found to show strong antitumor activity. However, few studies have yet investigated its role on pulmonary metastasis treated with this herb. To investigate the molecular mechanisms related to metastasis, we studied RPS-treated T739 mice using histopathology, immunohistochemistry and reverse transcription polymerase chain reaction. Apoptosis was measured by TUNEL assay. As a result, RPS inhibited tumor growth by inducing apoptosis and upregulated the expression of TIMP-2 and down-regulated the level of MMP-2 and MMP-9. In conclusion, RPS is a potent anticancer agent that elicits programmed cell death and inhibits metastases in murine lung adenocarcinoma in vivo.
