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

• Main Authors: Chien-Min Chen, Shu-Ching Hsieh, Chia-Liang Lin, Yu-Syun Lin, Jen-Pi Tsai, Yi-Hsien Hsieh
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2017-12-01
• Series: Cellular Physiology and Biochemistry
• Subjects: α-Mangostin; Renal carcinoma cells; Migration; Invasion; MMP-9
• Online Access: https://www.karger.com/Article/FullText/485582
• ISSN: 1015-8987; 1421-9778

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.