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

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Esophageal cancer (EC), particularly esophageal squamous cell carcinoma (ESCC), remains a significant global health concern with limited targeted therapies.
• Current treatment strategies for ESCC are insufficient, necessitating the exploration of novel therapeutic agents.

Purpose of the Study:

• To investigate the anti-cancer effects of Licochalcone B (Lico B) on ESCC cells.
• To elucidate the molecular mechanisms underlying Lico B's action, focusing on the Janus kinase (JAK)/STAT3 signaling pathway.

Main Methods:

• Cell viability assays were performed on KYSE450 and KYSE510 ESCC cell lines.
• Cell cycle progression and apoptosis were analyzed after Lico B treatment.
• Kinase assays, in vitro/ex vivo binding studies, and computational docking were used to identify Lico B's direct target.
• Western blotting was employed to assess the phosphorylation status of JAK2/STAT3 pathway proteins and Mcl-1 expression.

Main Results:

• Lico B significantly suppressed ESCC cell growth, induced G2/M cell cycle arrest, and promoted apoptosis.
• Lico B directly inhibited Janus kinase 2 (JAK2) activity, confirmed by biochemical assays and computational modeling.
• Lico B treatment led to decreased phosphorylation of STAT3 (at Y705 and S727) and reduced Mcl-1 expression, indicating JAK2/STAT3 pathway inhibition.

Conclusions:

• Licochalcone B demonstrates potent anti-cancer activity against ESCC by targeting the JAK2/STAT3 signaling pathway.
• Lico B effectively inhibits ESCC cell proliferation, induces cell cycle arrest, and triggers apoptosis.
• These findings highlight Licochalcone B as a promising therapeutic candidate for esophageal squamous cell carcinoma treatment.