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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway

Authors: Cheol-Jung Lee, Mee-Hyun Lee, Sun-Mi Yoo, Kyung-Il Choi, Ji-Hong Song, Jeong-Hoon Jang, Sei-Ryang Oh, Hyung-Won Ryu, Hye-Suk Lee, Young-Joon Surh, Yong-Yeon Cho

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Magnolin is a natural compound abundantly found in Magnolia flos, which has been traditionally used in oriental medicine to treat headaches, nasal congestion and anti-inflammatory reactions. Our recent results have demonstrated that magnolin targets the active pockets of ERK1 and ERK2, which are important signaling molecules in cancer cell metastasis. The aim of this study is to evaluate the effects of magnolin on cell migration and to further explore the molecular mechanisms involved.

Methods

Magnolin-mediated signaling inhibition was confirmed by Western blotting using RSK2+/+ and RSK2−/− MEFs, A549 and NCI-H1975 lung cancer cells, and by NF-κB and Cox-2 promoter luciferase reporter assays. Inhibition of cell migration by magnolin was examined by wound healing and/or Boyden Chamber assays using JB6 Cl41 and A549 human lung cancer cells. The molecular mechanisms involved in cell migration and epithelial-to-mesenchymal transition were determined by zymography, Western blotting, real-time PCR and immunocytofluorescence.

Results

Magnolin inhibited NF-κB transactivation activity by suppressing the ERKs/RSK2 signaling pathway. Moreover, magnolin abrogated the increase in EGF-induced COX-2 protein levels and wound healing. In human lung cancer cells such as A549 and NCI-H1975, which harbor constitutive active Ras and EGFR mutants, respectively, magnolin suppressed wound healing and cell invasion as seen by a Boyden chamber assay. In addition, it was observed that magnolin inhibited MMP-2 and −9 gene expression and activity. The knockdown or knockout of RSK2 in A549 lung cancer cells or MEFs revealed that magnolin targeting ERKs/RSK2 signaling suppressed epithelial-to-mesenchymal transition by modulating EMT marker proteins such as N-cadherin, E-cadherin, Snail, Vimentin and MMPs.

Conclusions

These results demonstrate that magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway.
Appendix
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Metadata
Title
Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway
Authors
Cheol-Jung Lee
Mee-Hyun Lee
Sun-Mi Yoo
Kyung-Il Choi
Ji-Hong Song
Jeong-Hoon Jang
Sei-Ryang Oh
Hyung-Won Ryu
Hye-Suk Lee
Young-Joon Surh
Yong-Yeon Cho
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1580-7

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