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Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance.
Toxicology. 2014 Aug 01; 322:23-33.T

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.

Authors+Show Affiliations

Natural Medicine Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea.Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea.Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, South Korea.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.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.Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, South Korea.Natural Medicine Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea.University of Ulsan, Department of Surgery, Gangneung Asan Hospital, Gangneung, Gangwon-do, South Korea.College of Korean Medicine, Gachon University, Seongnam, South Korea.Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Kwandong University College of Medicine, Seoul, South Korea. Electronic address: drug9054@naver.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24793912

Citation

Kim, Young-Joo, et al. "Stereospecific Effects of Ginsenoside 20-Rg3 Inhibits TGF-β1-induced Epithelial-mesenchymal Transition and Suppresses Lung Cancer Migration, Invasion and Anoikis Resistance." Toxicology, vol. 322, 2014, pp. 23-33.
Kim YJ, Choi WI, Jeon BN, et al. Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance. Toxicology. 2014;322:23-33.
Kim, Y. J., Choi, W. I., Jeon, B. N., Choi, K. C., Kim, K., Kim, T. J., Ham, J., Jang, H. J., Kang, K. S., & Ko, H. (2014). Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance. Toxicology, 322, 23-33. https://doi.org/10.1016/j.tox.2014.04.002
Kim YJ, et al. Stereospecific Effects of Ginsenoside 20-Rg3 Inhibits TGF-β1-induced Epithelial-mesenchymal Transition and Suppresses Lung Cancer Migration, Invasion and Anoikis Resistance. Toxicology. 2014 Aug 1;322:23-33. PubMed PMID: 24793912.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance. AU - Kim,Young-Joo, AU - Choi,Won-Il, AU - Jeon,Bu-Nam, AU - Choi,Kyung-Chul, AU - Kim,Kunhong, AU - Kim,Tae-Jin, AU - Ham,Jungyeob, AU - Jang,Hyuk Jai, AU - Kang,Ki Sung, AU - Ko,Hyeonseok, Y1 - 2014/05/02/ PY - 2014/03/17/received PY - 2014/04/05/revised PY - 2014/04/07/accepted PY - 2014/5/6/entrez PY - 2014/5/6/pubmed PY - 2014/8/26/medline KW - Epithelial–mesenchymal transition (EMT) KW - Ginsenoside 20(R)-Rg3 KW - Lung cancer KW - Metastasis KW - Transforming growth factor-beta 1 (TGF-β1) SP - 23 EP - 33 JF - Toxicology JO - Toxicology VL - 322 N2 - 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. SN - 1879-3185 UR - https://www.unboundmedicine.com/medline/citation/24793912/Stereospecific_effects_of_ginsenoside_20_Rg3_inhibits_TGF_β1_induced_epithelial_mesenchymal_transition_and_suppresses_lung_cancer_migration_invasion_and_anoikis_resistance_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(14)00079-1 DB - PRIME DP - Unbound Medicine ER -