20(R)-Ginsenoside Rg3 Influences Cancer Stem Cell Properties and the Epithelial-Mesenchymal Transition in Colorectal Cancer via the SNAIL Signaling Axis.

Cancer stem cells (CSCs) have been proposed as central drivers of cancer relapse in many cancers. In the present study, we investigated the inhibitory effect of 20(R)-Ginsenoside Rg3 (Rg3R), a major active component of ginseng saponin, on CSC-like cells and the Epithelial-Mesenchymal Transition (EMT) in colorectal cancer (CRC). The effects of ginsenoside Rg3R on the colony-forming, migration, invasion, and wound-healing abilities of CRC cells were determined in HT29 and SW620 cell lines in vitro. Further, ginsenoside Rg3R was given intraperitoneally at 5mg/kg of mouse body weight to check its effect on the metastasis of CRC cells in vivo. Ginsenoside Rg3R significantly inhibited CSC properties, but did not affect cell proliferation. Moreover, ginsenoside Rg3R treatment significantly inhibited the motility of CRC cells based on migration, invasion, and wound-healing assays. The inhibitory effects of ginsenoside Rg3R on CRC are potentially mediated by significant down-regulation of the expression of stemness genes and EMT markers in CRC cells in a SNAIL-dependent manner. Furthermore, ginsenoside Rg3R treatment decreased both the number and size of tumor nodules in the liver, lung, and kidney tissues in a metastasis mouse model. These findings highlighted the potential use of ginsenoside Rg3R in clinical applications for colorectal cancer treatment.

Phi LTH ，Wijaya YT ，Sari IN ，Kim KS ，Yang YG ，Lee MW ，Kwon HY ... -  《OncoTargets and Therapy》

The anti-metastatic effect of ginsenoside Rb2 in colorectal cancer in an EGFR/SOX2-dependent manner.

Ginsenoside Rb2, a saponin from Panax ginseng, has been shown to have many functions. However, the effect of ginsenoside Rb2 on the metastasis of colorectal cancer (CRC) remains unknown. CRC cell lines HT29 and SW620 were used to determine the effects of ginsenoside Rb2 on the colony-forming, migration, invasion, and wound-healing abilities of CRC cells in vitro. Further, ginsenoside Rb2 was given intraperitoneally at 5 mg/kg of mouse body weight to check its effect on the metastasis of CRC cells in vivo. Ginsenoside Rb2 decreased colony-forming ability, migration, invasion, and wound healing of CRC cells in vitro, although it did not affect cell proliferation. As a possible mechanism, we found that ginsenoside Rb2 down-regulated the expression of stemness and Epithelial-mesenchymal transition (EMT)-related genes via the EGFR/SOX2 signaling axis; these were partially rescued by either exogenous EGF treatment or ectopic expression of SOX2. More importantly, ginsenoside Rb2 significantly reduced the number of metastatic nodules in the livers, lungs, and kidneys in a mouse model of metastasis. These results suggest that ginsenoside Rb2 could be used to treat the metastasis of CRC therapeutically or as a supplement.

Phi LTH ，Wijaya YT ，Sari IN ，Yang YG ，Lee YK ，Kwon HY ... -  《Cancer Medicine》

Ginsenoside Rd Inhibits the Metastasis of Colorectal Cancer via Epidermal Growth Factor Receptor Signaling Axis.

Ginsenoside Rd is a saponin from ginseng and has been reported to have various biological activities. However, the effect of ginsenoside Rd on the metastasis of colorectal cancer (CRC) remains unknown. Here, we found that ginsenoside Rd decreased the colony-forming ability, migration, invasion, and wound-healing abilities of CRC cells, although it did not affect cell proliferation. In addition, using an inverse-docking assay, we found that ginsenoside Rd bound to epidermal growth factor receptor (EGFR) with a high binding affinity, inducing the downregulation of stemness- and epithelial-mesenchymal transition-related genes; these were partially rescued by either exogenous EGF treatment or ectopic expression of SOX2. Furthermore, ginsenoside Rd significantly decreased the number and size of tumor metastasis nodules in the livers, lungs, and kidneys of mouse model of metastasis. © 2018 IUBMB Life, 71(5):601-610, 2019.

Phi LTH ，Sari IN ，Wijaya YT ，Kim KS ，Park K ，Cho AE ，Kwon HY ... -  《-》

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

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.

Kim YJ ，Choi WI ，Jeon BN ，Choi KC ，Kim K ，Kim TJ ，Ham J ，Jang HJ ，Kang KS ，Ko H ... -  《-》

Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4.

Tian L ，Shen D ，Li X ，Shan X ，Wang X ，Yan Q ，Liu J ... -  《Oncotarget》