Kim, Young-Joo Choi, Won-Il Jeon, Bu-Nam Choi, Kyung-Chul Kim, Kunhong Kim, Tae-Jin Ham, Jungyeob Jang, Hyuk Jai Kang, Ki Sung Ko, Hyeonseok 2024-01-20T09:03:57Z 2024-01-20T09:03:57Z 2021-09-05 2014-08-01 0300-483X https://pubs.kist.re.kr/handle/201004/126490 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-beta 1) 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-beta 1-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-beta 1-induced EMT. 20(R)-Rg3 also inhibited the TGF-beta 1-induced increase in cell migration, invasion, and anoikis resistance of A549 lung cancer cells. Additionally, 20(R)-Rg3 markedly inhibited TGF-beta 1-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-beta 1-induced EMT. (C) 2014 Elsevier Ireland Ltd. All rights reserved. English ELSEVIER IRELAND LTD TGF-BETA TRANSFORMING GROWTH-FACTOR-BETA-1 CADHERIN EXPRESSION CEREBRAL-ISCHEMIA TUMOR-METASTASIS SNAIL MATRIX CELLS RG(3) GENISTEIN Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-beta 1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance Article 10.1016/j.tox.2014.04.002 1 TOXICOLOGY, v.322, pp.23 - 33 TOXICOLOGY 322 23 33 scie scopus 000338978800003 2-s2.0-84901228851 Pharmacology & Pharmacy Toxicology Pharmacology & Pharmacy Toxicology Article TGF-BETA TRANSFORMING GROWTH-FACTOR-BETA-1 CADHERIN EXPRESSION CEREBRAL-ISCHEMIA TUMOR-METASTASIS SNAIL MATRIX CELLS RG(3) GENISTEIN Ginsenoside 20(R)-Rg3 Epithelial-mesenchymal transition (EMT) Transforming growth factor-beta 1 (TGF-beta 1) Lung cancer Metastasis