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Toxicology. 2014 Aug 1;322:23-33. doi: 10.1016/j.tox.2014.04.002. Epub 2014 May 2.

Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance.

Author information

1
Natural Medicine Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea.
2
Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea.
3
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea; Department of Pharmacology, University of Ulsan College of Medicine, Seoul, South Korea.
4
Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea; Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, South Korea.
5
Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, South Korea.
6
University of Ulsan, Department of Surgery, Gangneung Asan Hospital, Gangneung, Gangwon-do, South Korea.
7
College of Korean Medicine, Gachon University, Seongnam, South Korea.
8
Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Kwandong University College of Medicine, Seoul, South Korea. Electronic address: drug9054@naver.com.

Abstract

The epithelial-mesenchymal transition (EMT) is a pivotal cellular process during which epithelial polarized cells become motile mesenchymal-appearing cells, which, in turn, promotes the metastatic potential of cancer. Ginseng is a perennial plant belonging to the genus Panax that exhibits a wide range of pharmacological and physiological activities. Ginsenosides 20-Rg3, which is the active component of ginseng, has various medical effects, such as anti-tumorigenic, anti-angiogenesis, and anti-fatiguing activities. In addition, ginsenosides 20(S)-Rg3 and 20(R)-Rg3 are epimers, and this epimerization is produced by steaming. However, the possible role of 20(S)-Rg3 and 20(R)-Rg3 in the EMT is unclear. We investigated the effect of 20(S)-Rg3 and 20(R)-Rg3 on the EMT. Transforming growth factor-beta 1 (TGF-β1) induces the EMT to promote lung adenocarcinoma migration, invasion, and anoikis resistance. To understand the repressive role of 20(S)-Rg3 and 20(R)-Rg3 in lung cancer migration, invasion, and anoikis resistance, we investigated the potential use of 20(S)-Rg3 and 20(R)-Rg3 as inhibitors of TGF-β1-induced EMT development in A549 lung cancer cells in vitro. Here, we show that 20(R)-Rg3, but not 20(S)-Rg3, markedly increased expression of the epithelial marker E-cadherin and repressed Snail upregulation and expression of the mesenchymal marker vimentin during initiation of the TGF-β1-induced EMT. 20(R)-Rg3 also inhibited the TGF-β1-induced increase in cell migration, invasion, and anoikis resistance of A549 lung cancer cells. Additionally, 20(R)-Rg3 markedly inhibited TGF-β1-regulated matrix metalloproteinase-2 and activation of Smad2 and p38 mitogen activated protein kinase. Taken together, our findings provide new evidence that 20(R)-Rg3 suppresses lung cancer migration, invasion, and anoikis resistance in vitro by inhibiting the TGF-β1-induced EMT.

KEYWORDS:

Epithelial–mesenchymal transition (EMT); Ginsenoside 20(R)-Rg3; Lung cancer; Metastasis; Transforming growth factor-beta 1 (TGF-β1)

PMID:
24793912
DOI:
10.1016/j.tox.2014.04.002
[Indexed for MEDLINE]

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