Protopanaxatriol ginsenoside Rh1 inhibits the expression of matrix metalloproteinases and the in vitro invasion/migration of human astroglioma cells.

Abstract

Malignant gliomas are the most common and fatal brain tumors in adults. In particular, the strong invasiveness of glioma cells into the normal brain tissue makes eradication of glioma very difficult. Matrix metalloproteinases (MMPs) play a pivotal role in glioma invasion, and thus controlling MMP expression has been suggested as an important therapeutic target for brain tumors. In the present study, we investigated the effect of protopanaxatriol ginsenoside Rh1 on MMP expressions in human astroglioma U87MG and U373MG cells. RT-PCR analysis showed that Rh1 inhibits the mRNA expressions of MMP-1, -3, and -9 in PMA-stimulated U87MG and U373MG cells. Rh1 also suppressed the promoter activities of MMP-1, -3 and -9. The ELISA, Western blot, and zymographic analyses revealed that Rh1 inhibits the protein expression and/or enzymatic activity of MMP-1, -3 and -9. In accordance with the strong inhibitory effects of Rh1 on MMPs, Rh1 efficiently inhibited the invasion and migration of U87MG and U373MG glioma cells as demonstrated by Matrigel invasion assay and wound healing assay. Further mechanistic studies revealed that Rh1 inhibits MAPK and PI3K/Akt signaling pathways and downstream transcription factors such as NF-κB and AP-1, which play an important role in MMP gene expressions. The data collectively suggest that ginsenoside Rh1 may have a therapeutic potential for malignant gliomas.

• Authors: Ji-Sun Jung, Jung-Hyuck Ahn, Thi Kim Le, Dong-Hyun Kim, Hee-Sun Kim
• Journal: Neurochemistry international (Neurochem Int) Vol. 63 Issue 2 Pg. 80-6 (Aug 2013) ISSN: 1872-9754 [Electronic] England
• PMID: 23684955 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• DNA Primers
• Protease Inhibitors
• RNA, Messenger
• Sapogenins
• protopanaxatriol
• Matrix Metalloproteinases

Topics

• Astrocytoma (enzymology, pathology)
• Base Sequence
• Blotting, Western
• Brain Neoplasms (enzymology, pathology)
• Cell Line, Tumor
• DNA Primers
• Enzyme-Linked Immunosorbent Assay
• Humans
• Matrix Metalloproteinases (drug effects, genetics, metabolism)
• Neoplasm Invasiveness (prevention & control)
• Neoplasm Metastasis (prevention & control)
• Protease Inhibitors (pharmacology)
• RNA, Messenger (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Sapogenins (pharmacology)