Ginsenosides Rk1 and Rg5 Inhibit Transforming Growth Factor-β1-induced Epithelial-mesenchymal Transition and Suppress Migration, Invasion, Anoikis Resistance, and Development of Stem-like Features in Lung Cancer

Overview

Journal J Ginseng Res

Date 2021 Jan 13

PMID 33437165

Citations 38

Authors

Hyunhee Kim

Pilju Choi

Taejung Kim

Youngseok Kim

Bong Geun Song

Young-Tae Park

Seon-Jun Choi

Cheol Hee Yoon

Won-Chul Lim

Hyeonseok Ko

Jungyeob Ham

Affiliations

Soon will be listed here.

Abstract

Background: Lung cancer has a high incidence worldwide, and most lung cancer-associated deaths are attributable to cancer metastasis. Although several medicinal properties of Meyer have been reported, the effect of ginsenosides Rk1 and Rg5 on epithelial-mesenchymal transition (EMT) stimulated by transforming growth factor beta 1 (TGF- β1) and self-renewal in A549 cells is relatively unknown.

Methods: We treated TGF-β1 or alternatively Rk1 and Rg5 in A549 cells. We used western blot analysis, real-time polymerase chain reaction (qPCR), wound healing assay, Matrigel invasion assay, and anoikis assays to determine the effect of Rk1 and Rg5 on TGF-mediated EMT in lung cancer cell. In addition, we performed tumorsphere formation assays and real-time PCR to evaluate the stem-like properties.

Results: EMT is induced by TGF-β1 in A549 cells causing the development of cancer stem-like features. Expression of E-cadherin, an epithelial marker, decreased and an increase in vimentin expression was noted. Cell mobility, invasiveness, and anoikis resistance were enhanced with TGF-β1 treatment. In addition, the expression of stem cell markers, CD44, and CD133, was also increased. Treatment with Rk1 and Rg5 suppressed EMT by TGF-β1 and the development of stemness in a dose-dependent manner. Additionally, Rk1 and Rg5 markedly suppressed TGF-β1-induced metalloproteinase-2/9 (MMP2/9) activity, and activation of Smad2/3 and nuclear factor kappa B/extra-cellular signal regulated kinases (NF-kB/ERK) pathways in lung cancer cells.

Conclusions: Rk1 and Rg5 regulate the EMT inducing TGF-β1 by suppressing the Smad and NF-κB/ERK pathways (non-Smad pathway).

Citing Articles

Metabolic reprogramming and signaling adaptations in anoikis resistance: mechanisms and therapeutic targets.

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Fang X, Wei M, Liu X, Lu L, Liu G Transl Cancer Res. 2024; 13(10):5458-5472.

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