Abstract Title:

Janus kinase 2 inhibition by Licochalcone B suppresses esophageal squamous cell carcinoma growth.

Abstract Source:

Phytother Res. 2020 Mar 6. Epub 2020 Mar 6. PMID: 32144852

Abstract Author(s):

Mengqiu Song, Goo Yoon, Joon-Seok Choi, Eunae Kim, Xuejiao Liu, Ha-Na Oh, Jung-Il Chae, Mee-Hyun Lee, Jung-Hyun Shim

Article Affiliation:

Mengqiu Song


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.

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