Pregnane alkaloid salonine B targets BCL9 to inhibit hepatocellular carcinoma-Source Data

Bioinformatic analyses of TCGA and GEO databases revealed that BCL9 was significantly upregulated in HCC tissues, and high BCL9 expression was closely associated with poor prognosis of patients. By establishing stably transfected BCL9-knockdown SK-Hep-1 and BEL-7402 cell lines, we demonstrated that silencing BCL9 markedly suppressed HCC cell proliferation.

Based on the crystal structure of the BCL9/β-catenin complex, a computer-aided virtual screening model was constructed, leading to the identification of pregnane alkaloid salonine B, a natural product from Sarcococca saligna. Surface plasmon resonance analysis confirmed that salonine B directly interacts with BCL9 protein in vitro. Cell-based assays, such as MTT and Transwell migration assays, demonstrated that salonine B significantly inhibited the cell proliferation and migration of HCC cells in a BCL9-dependent manner.