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Cell Physiol Biochem. 2017;44(4):1460-1470. doi: 10.1159/000485582. Epub 2017 Dec 1.

Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by Targeting MEK/ERK Expression and MMP-9 Transcription Activity.

Author information

1
Division of Neurosurgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.
2
School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
3
School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
4
Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
5
School of Medicine, Tzu Chi University, Hualien, Taiwan.
6
Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
7
Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
8
Clinical laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.

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.

KEYWORDS:

Invasion; MMP-9; Migration; Renal carcinoma cells; α-Mangostin

PMID:
29190630
DOI:
10.1159/000485582
[Indexed for MEDLINE]
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