Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by Targeting MEK/ERK Expression and MMP-9 Transcription Activity.
Cell Physiol Biochem
; 44(4): 1460-1470, 2017.
Article
em En
| MEDLINE
| ID: mdl-29190630
ABSTRACT
BACKGROUND/AIMS:
α-mangostin has anti-carcinogenic effects against several cancers. We investigated the molecular mechanism of this compound on the metastasis of human renal carcinoma cells.METHODS:
Cell viability was measured using the MTT assay, and cell cycle distribution using flow cytometry. A Matrigel-based assay was used to measure in vitro cell migration and invasion. MAPK-related proteins and matrix metalloproteinase (MMP)-9 and MMP-2 expression were measured by western blotting, and MMP2/-9 activities were determined by gelatin zymography. RT-qPCR and a luciferase assay were used to examine the transcriptional activity of MMP-9.RESULTS:
α-mangostin inhibited the migration and invasion of RCC cells in a dose-dependent manner, but had no evident cytotoxic effects. Treatment of 786-O cells with α-mangostin inhibited activation of MEK and ERK. Treatment with a specific MEK inhibitor (U0126) enhanced the inhibitory effects of α-mangostin on cell migration and invasion, and the phosphorylation of ERK and MEK. Moreover, α-mangostin inhibited the expression of the MMP-9 mRNA levels as well as the activity of MMP-9 promoter, and these suppressive effects were further enhanced by U0126.CONCLUSIONS:
Our results suggest that α-mangostin suppresses cell migration and invasion via MEK/ERK/MMP9 pathway, and might be a promising anti-metastatic agent against human renal cell carcinoma.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Transdução de Sinais
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Anticarcinógenos
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Metaloproteinase 9 da Matriz
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MAP Quinase Quinase Quinases
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Xantonas
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MAP Quinases Reguladas por Sinal Extracelular
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Taiwan