22-O-(N-Boc-L-glycine) ester of renieramycin M inhibits migratory activity and suppresses epithelial-mesenchymal transition in human lung cancer cells.
EMT
Human lung cancer cells
Invasion
Marine alkaloid
Migration
Renieramycin M
Journal
Journal of natural medicines
ISSN: 1861-0293
Titre abrégé: J Nat Med
Pays: Japan
ID NLM: 101518405
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
03
03
2021
accepted:
04
07
2021
pubmed:
22
7
2021
medline:
26
11
2021
entrez:
21
7
2021
Statut:
ppublish
Résumé
The incidence of metastasis stage crucially contributes to high recurrence and mortality rate in lung cancer patients. Unfortunately, no available treatment inhibits migration, a key metastasis process in lung cancer. In this study, the effect of 22-O-(N-Boc-L-glycine) ester of renieramycin M (22-Boc-Gly-RM), a semi-synthetic amino ester derivative of bistetrahydroisoquinolinequinone alkaloid isolated from Xestospongia sp., on migratory behavior of human lung cancer cells was investigated. Following 24 h of treatment, 22-Boc-Gly-RM at non-toxic concentrations (0.5-1 μM) effectively restrained motility of human lung cancer H460 cells assessed through wound healing, transwell migration, and multicellular spheroid models. The capability to invade through matrix component was also repressed in H460 cells cultured with 0.1-1 µM 22-Boc-Gly-RM. The dose-dependent reduction of phalloidin-stained actin stress fibers corresponded with the downregulated Rac1-GTP level presented via western blot analysis in 22-Boc-Gly-RM-treated cells. Treatment with 0.1-1 μM of 22-Boc-Gly-RM obviously caused suppression of p-FAK/p-Akt signal and consequent inhibition of epithelial-to-mesenchymal transition (EMT), which was evidenced with augmented level of E-cadherin and reduction of N-cadherin expression. The alteration of invasion-related proteins in 22-Boc-Gly-RM-treated H460 cells was indicated by the diminution of matrix metalloproteinases (MT1-MMP, MMP-2, MMP-7, and MMP-9), as well as the upregulation of tissue inhibitors of metalloproteinases (TIMP), TIMP2, and TIMP3. Thus, 22-Boc-Gly-RM is a promising candidate for anti-metastasis treatment in lung cancer through inhibition of migratory features associated with suppression on EMT.
Identifiants
pubmed: 34287745
doi: 10.1007/s11418-021-01549-3
pii: 10.1007/s11418-021-01549-3
doi:
Substances chimiques
Esters
0
Tetrahydroisoquinolines
0
renieramycin M
0
Glycine
TE7660XO1C
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
949-966Subventions
Organisme : Chulalongkorn University
ID : CU_GR_62_20_33_01
Organisme : Chulalongkorn University
ID : 90th Anniversary of Chulalongkorn University
Organisme : National Research Council of Thailand
ID : RSA 6280009
Informations de copyright
© 2021. The Japanese Society of Pharmacognosy.
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