The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis
- Author:
- Zhou R., Yang Y., Park S.-Y., Nguyen T.T., Seo Y.-W., Lee K.H., Lee J.H., Kim K.K., Hur J.-S. & Kim H.
- Year:
- 2017
- Journal:
- Scientific Reports
- Pages:
- 7:8136 [13 p.]
- Url:
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.
- Id:
- 29936
- Submitter:
- zdenek
- Post_time:
- Monday, 12 November 2018 10:53