Gossypin inhibits gastric cancer growth by direct targeting of AURKA and RSK2.
AURKA
RSK2
apoptosis
gastric cancer
gossypin
Journal
Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486
Informations de publication
Date de publication:
Mar 2019
Mar 2019
Historique:
received:
23
08
2018
revised:
11
11
2018
accepted:
15
11
2018
pubmed:
12
12
2018
medline:
14
6
2019
entrez:
12
12
2018
Statut:
ppublish
Résumé
Gossypin is a flavone extracted from Hibiscus vitifolius, which has been reported to exhibit anti-inflammatory, antioxidant, and anticancer activities. However, the anticancer properties of gossypin and its molecular mechanism of action against gastric cancer have not been fully investigated. In the present study, we report that gossypin is an Aurora kinase A (AURKA) and RSK2 inhibitor that suppresses gastric cancer growth. Gossypin attenuated anchorage-dependent and anchorage-independent gastric cancer cell growth as well as cell migration. Based on the results of in vitro screening and cell-based assays, gossypin directly binds to and inhibits AURKA and RSK2 activities and their downstream signaling proteins. Gossypin decreased S phase and increased G2/M phase cell cycle arrest by reducing the expression of cyclin A2 and cyclin B1 and the phosphorylation of the CDC protein. Additionally, gossypin also induced intrinsic apoptosis by activating caspases and PARP and increasing the expression of cytochrome c. Our results demonstrate that gossypin is an AURKA and RSK2 inhibitor that could be useful for treating gastric cancer.
Identifiants
pubmed: 30536456
doi: 10.1002/ptr.6253
pmc: PMC6416069
mid: NIHMS998512
doi:
Substances chimiques
Antineoplastic Agents
0
Flavonoids
0
gossypin
A3Q367XWX9
Aurora Kinase A
EC 2.7.11.1
Ribosomal Protein S6 Kinases, 90-kDa
EC 2.7.11.1
ribosomal protein S6 kinase, 90kDa, polypeptide 3
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
640-650Subventions
Organisme : National Natural Science Foundation of China
ID : 81572812
Organisme : National Institutes of Health
ID : CA187027
Organisme : National Institutes of Health
ID : CA196639
Organisme : NCI NIH HHS
ID : R01 CA187027
Pays : United States
Organisme : Key Program of Henan Province, China
ID : 161100510300
Organisme : NCI NIH HHS
ID : R01 CA196639
Pays : United States
Informations de copyright
© 2018 John Wiley & Sons, Ltd.
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