Butein suppresses hepatocellular carcinoma growth via modulating Aurora B kinase activity

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Aurora B kinase is overexpressed in various cancers, including hepatocellular carcinoma (HCC), making it a promising therapeutic target.
• Butein, a chalcone from Rhus cerniciflua, exhibits antitumor properties in preclinical studies.

Purpose of the Study:

• To investigate if Aurora B kinase is the direct molecular target of butein's antitumor activity in HCC.
• To validate the therapeutic potential of butein in HCC models.

Main Methods:

• Quantitative analysis of Aurora B expression in HCC cell lines and tumor tissues.
• RNA interference (shRNA) to knockdown Aurora B expression.
• In vitro kinase assays and computer docking to assess butein-Aurora B interaction.
• Cell cycle analysis and apoptosis assays.
• In vivo studies using HCC xenograft models in nude mice.

Main Results:

• Aurora B was significantly overexpressed in HCC cells and tissues compared to normal controls.
• Knockdown of Aurora B inhibited HCC cell proliferation, colony formation, and tumor growth in vivo.
• Butein directly bound to Aurora B and inhibited its kinase activity, leading to G2/M cell cycle arrest and apoptosis.
• Butein's antitumor effects were diminished in Aurora B knockdown cells.
• Oral administration of butein suppressed HCC xenograft growth and reduced proliferation markers (Ki67, p-histone H3) in vivo.

Conclusions:

• Aurora B is a direct molecular target of butein in hepatocellular carcinoma.
• Butein demonstrates significant antitumor efficacy in HCC by inhibiting Aurora B kinase activity.
• These findings support butein as a potential therapeutic agent for HCC targeting Aurora B.