Tags

Type your tag names separated by a space and hit enter

Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway.
BMC Cancer. 2015 Aug 08; 15:576.BC

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.

Authors+Show Affiliations

College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-743, Republic of Korea. veritas0613@naver.com.College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-743, Republic of Korea. mhyun_lee@catholic.ac.kr.College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-743, Republic of Korea. apple_ma@naver.com.College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-743, Republic of Korea. luna239@naver.com.College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-743, Republic of Korea. xlzlzl1103@gmail.com.College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-743, Republic of Korea. jhjang1717@gmail.com. College of Pharmacy, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea. jhjang1717@gmail.com.Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, ChungBuk, 363-883, Republic of Korea. seiryang@kribb.re.kr.Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, ChungBuk, 363-883, Republic of Korea. ryuhw@kribb.re.kr.College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-743, Republic of Korea. sianalee@catholic.ac.kr.College of Pharmacy, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea. surh@plaza.snu.ac.kr.College of Pharmacy, The Catholic University of Korea, 43, Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420-743, Republic of Korea. yongyeon@catholic.ac.kr.

Pub Type(s)

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

Language

eng

PubMed ID

26253302

Citation

Lee, Cheol-Jung, et al. "Magnolin Inhibits Cell Migration and Invasion By Targeting the ERKs/RSK2 Signaling Pathway." BMC Cancer, vol. 15, 2015, p. 576.
Lee CJ, Lee MH, Yoo SM, et al. Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway. BMC Cancer. 2015;15:576.
Lee, C. J., Lee, M. H., Yoo, S. M., Choi, K. I., Song, J. H., Jang, J. H., Oh, S. R., Ryu, H. W., Lee, H. S., Surh, Y. J., & Cho, Y. Y. (2015). Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway. BMC Cancer, 15, 576. https://doi.org/10.1186/s12885-015-1580-7
Lee CJ, et al. Magnolin Inhibits Cell Migration and Invasion By Targeting the ERKs/RSK2 Signaling Pathway. BMC Cancer. 2015 Aug 8;15:576. PubMed PMID: 26253302.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Magnolin inhibits cell migration and invasion by targeting the ERKs/RSK2 signaling pathway. AU - Lee,Cheol-Jung, AU - Lee,Mee-Hyun, AU - Yoo,Sun-Mi, AU - Choi,Kyung-Il, AU - Song,Ji-Hong, AU - Jang,Jeong-Hoon, AU - Oh,Sei-Ryang, AU - Ryu,Hyung-Won, AU - Lee,Hye-Suk, AU - Surh,Young-Joon, AU - Cho,Yong-Yeon, Y1 - 2015/08/08/ PY - 2015/01/15/received PY - 2015/07/27/accepted PY - 2015/8/9/entrez PY - 2015/8/9/pubmed PY - 2016/3/25/medline SP - 576 EP - 576 JF - BMC cancer JO - BMC Cancer VL - 15 N2 - 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. SN - 1471-2407 UR - https://www.unboundmedicine.com/medline/citation/26253302/Magnolin_inhibits_cell_migration_and_invasion_by_targeting_the_ERKs/RSK2_signaling_pathway_ L2 - https://bmccancer.biomedcentral.com/articles/10.1186/s12885-015-1580-7 DB - PRIME DP - Unbound Medicine ER -