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Environ Toxicol. 2017 Nov;32(11):2360-2370. doi: 10.1002/tox.22449. Epub 2017 Jul 19.

β-mangostin suppresses human hepatocellular carcinoma cell invasion through inhibition of MMP-2 and MMP-9 expression and activating the ERK and JNK pathways.

Author information

1
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
2
Department of Critical Care Medicine, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
3
Department of Emergency Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
4
Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
5
School of Medical Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan.
6
Department of Internal Medicine, Division of Gastroenterology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
7
Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
8
Department of Neurosurgery, Tungs'Taichung MetroHarbor Hospital, Taichung, Taiwan.
9
Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
10
Clinical laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
11
Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan.

Abstract

β-mangostin is a dietary xanthone that has been reported to have the anticancer properties in some human cancer cell types. However, the antimetastatic effect and molecular mechanism of β-mangostin action in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we found that β-mangostin did not induce cytotoxicity in human HCC cells (SK-Hep-1, Huh-7 and HA22T/VGH cells). β-mangostin could inhibit migration and invasion of human HCC cells. Meanwhile, β-mangostin significantly decreased the protein activities and expression of matrix metalloproteinase (MMP)-2 and MMP-9 via increasing the activation of MEK1/2, ERK1/2, MEK4 and JNK1/2 signaling pathways. Furthermore, using specific inhibitor for ERK1/2 (PD98059) and JNK1/2 (JNKII) significantly restored the expression of MMP-2/-9 and invasion by β-mangostin treatment in Huh-7 cells. In addition, β-mangostin effectively restored the protein levels and transcription activity of MMP-2 and MMP-9 in siERK or siJNK-transfected Huh-7 cells, concomitantly with promotion on cell migration and invasion. Taken together, these findings are the first to demonstrate the antimetastatic activity of β-mangostin against human HCC cells, which may act as a promising therapeutic agent for the treatment of HCC.

KEYWORDS:

MMP-2; MMP-9; hepatocellular carcinoma cell; invasion; migration; β-Mangostin

PMID:
28722351
DOI:
10.1002/tox.22449
[Indexed for MEDLINE]

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