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Molecules. 2018 Jul 2;23(7). pii: E1601. doi: 10.3390/molecules23071601.

Bergamottin Suppresses Metastasis of Lung Cancer Cells through Abrogation of Diverse Oncogenic Signaling Cascades and Epithelial-to-Mesenchymal Transition.

Author information

1
Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. gokjh1647@gmail.com.
2
Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. hanisanam@hanmail.net.
3
Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. jyum@khu.ac.kr.
4
KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Korea. shjung507@gmail.com.
5
Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam. gautam.sethi@tdt.edu.vn.
6
Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam. gautam.sethi@tdt.edu.vn.
7
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore. phcgs@nus.edu.sg.
8
Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea. ksahn@khu.ac.kr.
9
KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Korea. ksahn@khu.ac.kr.

Abstract

Bergamottin (BGM) is a naturally occurring furanocoumarin and is known to inhibit the growth of tumor cells. However, there is no available evidence that BGM has an inhibitory effect on cancer metastasis, specifically on the epithelial-to-mesenchymal transition (EMT) process in the malignant cells. Here we aimed to evaluate the antimetastatic potential of BGM in human lung adenocarcinoma cells. Our results demonstrate that BGM can block EMT, and observed inhibition was accompanied by downregulation of fibronectin, vimentin, N-cadherin, twist and snail expression, and upregulation of occludin and E-cadherin. Interestingly, transforming growth factor-β (TGF-β)-induced upregulation of fibronectin, vimentin, N-cadherin, twist and snail, and downregulation of occludin and E-cadherin, were abrogated by BGM treatment. Moreover, the treatment of BGM repressed TGF-β-induced cell invasive potential. BGM treatment also inhibited multiple oncogenic cascades such as PI3K/Akt/mTOR. Overall, the results demonstrate the potential antimetastatic activity of BGM against lung cancer cells.

KEYWORDS:

EMT; bergamottin; lung cancer; metastasis

PMID:
30004418
PMCID:
PMC6100248
DOI:
10.3390/molecules23071601
[Indexed for MEDLINE]
Free PMC Article

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