Janus kinase 2 inhibition by Licochalcone B suppresses esophageal squamous cell carcinoma growth.
Phytother Res
; 34(8): 2032-2043, 2020 Aug.
Article
en En
| MEDLINE
| ID: mdl-32144852
ABSTRACT
Esophageal cancer (EC) is one of the leading causes to cancer death in the worldwide and major population of EC is esophageal squamous cell carcinoma (ESCC). Still, ESCC-targeted therapy has not been covered yet. In the present study we have identified that Licochalcone B (Lico B) inhibited the ESCC growth by directly blocking the Janus kinase (JAK) 2 activity and its downstream signaling pathway. Lico B suppressed KYSE450 and KYSE510 ESCC cell growth, arrested cell cycle at G2/M phase and induced apoptosis. Direct target of Lico B was identified by kinase assay and verified with in vitro and ex vivo binding. Computational docking model predicted for Lico B interaction to ATP-binding pocket of JAK2. Furthermore, treatment of JAK2 clinical medicine AZD1480 to ESCC cells showed similar tendency with Lico B. Thus, JAK2 downstream signaling proteins phosphorylation of STAT3 at Y705 and S727 as well as STAT3 target protein Mcl-1 expression was decreased with treatment of Lico B. Our results suggest that Lico B inhibits ESCC cell growth, arrests cell cycle and induces apoptosis, revealing the underlying mechanism involved in JAK2/STAT3 signaling pathways after Lico B treatment. It might provide potential role of Lico B in the treatment of ESCC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Chalconas
/
Janus Quinasa 2
/
Carcinoma de Células Escamosas de Esófago
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Phytother Res
Asunto de la revista:
TERAPIAS COMPLEMENTARES
Año:
2020
Tipo del documento:
Article
País de afiliación:
China