The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis

Abstract Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranori...

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Autores principales:	Rui Zhou, Yi Yang, So-Yeon Park, Thanh Thi Nguyen, Young-Woo Seo, Kyung Hwa Lee, Jae Hyuk Lee, Kyung Keun Kim, Jae-Seoun Hur, Hangun Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6fd35efdbd7047b4993d3c968d458092
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spelling	oai:doaj.org-article:6fd35efdbd7047b4993d3c968d4580922021-12-02T15:06:16ZThe lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis10.1038/s41598-017-08225-12045-2322https://doaj.org/article/6fd35efdbd7047b4993d3c968d4580922017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08225-1https://doaj.org/toc/2045-2322Abstract Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranorin was identified as an active subcomponent of this extract. Atranorin suppressed β-catenin-mediated TOPFLASH activity by inhibiting the nuclear import of β-catenin and downregulating β-catenin/LEF and c-jun/AP-1 downstream target genes such as CD44, cyclin-D1 and c-myc. Atranorin decreased KAI1 C-terminal interacting tetraspanin (KITENIN)-mediated AP-1 activity and the activity of the KITENIN 3′-untranslated region. The nuclear distribution of the AP-1 transcriptional factor, including c-jun and c-fos, was suppressed in atranorin-treated cells, and atranorin inhibited the activity of Rho GTPases including Rac1, Cdc42, and RhoA, whereas it had no effect on epithelial-mesenchymal transition markers. STAT-luciferase activity and nuclear STAT levels were decreased, whereas total STAT levels were moderately reduced. The human cell motility and lung cancer RT² Profiler PCR Arrays identified additional atranorin target genes. Atranorin significantly inhibited tumorigenesis in vitro and in vivo. Taken together, our results indicated that E. vexans and its subcomponent atranorin may inhibit lung cancer cell motility and tumorigenesis by affecting AP-1, Wnt, and STAT signaling and suppressing RhoGTPase activity.Rui ZhouYi YangSo-Yeon ParkThanh Thi NguyenYoung-Woo SeoKyung Hwa LeeJae Hyuk LeeKyung Keun KimJae-Seoun HurHangun KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rui Zhou Yi Yang So-Yeon Park Thanh Thi Nguyen Young-Woo Seo Kyung Hwa Lee Jae Hyuk Lee Kyung Keun Kim Jae-Seoun Hur Hangun Kim The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis
description	Abstract Lichens are symbiotic organisms that produce various secondary metabolites. Here, different lichen extracts were examined to identify secondary metabolites with anti-migratory activity against human lung cancer cells. Everniastrum vexans had the most potent inhibitory activity, and atranorin was identified as an active subcomponent of this extract. Atranorin suppressed β-catenin-mediated TOPFLASH activity by inhibiting the nuclear import of β-catenin and downregulating β-catenin/LEF and c-jun/AP-1 downstream target genes such as CD44, cyclin-D1 and c-myc. Atranorin decreased KAI1 C-terminal interacting tetraspanin (KITENIN)-mediated AP-1 activity and the activity of the KITENIN 3′-untranslated region. The nuclear distribution of the AP-1 transcriptional factor, including c-jun and c-fos, was suppressed in atranorin-treated cells, and atranorin inhibited the activity of Rho GTPases including Rac1, Cdc42, and RhoA, whereas it had no effect on epithelial-mesenchymal transition markers. STAT-luciferase activity and nuclear STAT levels were decreased, whereas total STAT levels were moderately reduced. The human cell motility and lung cancer RT² Profiler PCR Arrays identified additional atranorin target genes. Atranorin significantly inhibited tumorigenesis in vitro and in vivo. Taken together, our results indicated that E. vexans and its subcomponent atranorin may inhibit lung cancer cell motility and tumorigenesis by affecting AP-1, Wnt, and STAT signaling and suppressing RhoGTPase activity.
format	article
author	Rui Zhou Yi Yang So-Yeon Park Thanh Thi Nguyen Young-Woo Seo Kyung Hwa Lee Jae Hyuk Lee Kyung Keun Kim Jae-Seoun Hur Hangun Kim
author_facet	Rui Zhou Yi Yang So-Yeon Park Thanh Thi Nguyen Young-Woo Seo Kyung Hwa Lee Jae Hyuk Lee Kyung Keun Kim Jae-Seoun Hur Hangun Kim
author_sort	Rui Zhou
title	The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis
title_short	The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis
title_full	The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis
title_fullStr	The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis
title_full_unstemmed	The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis
title_sort	lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6fd35efdbd7047b4993d3c968d458092
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The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis

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