Purpose: To investigate the effect of excisanin A on human hepatocellular carcinoma cells as well as to elucidate its mechanism of action.
Methods: Molecular docking was used to determine the binding characteristics of excisanin A to HIF-1α protein. The transcriptional activation and viability of excisanin A were assessed using Luciferase reporter and MTT assay. The HIF-1α protein in the nucleus was assayed using western blot and immunofluorescence. HIF-1α and VEGF mRNA levels were evaluated using reverse-transcription polymerase chain reaction (RT-PCR). Cell proliferation was determined by flow cytometry, as well as by EdU and clonogenic assays. In vivo tumor growth was assessed in a murine xenograft model of SKHep1 cells.
Results: Excisanin A inhibited HIF-1α transcriptional activation, as well as HIF-1α protein synthesis (p < 0.001). Excisanin A also reduced VEGF protein and mRNA expressions (p < 0.001). In addition, the compound inhibited the proliferation of hepatocellular carcinoma cells. and tumor growth in the xenograft tumor model.
Conclusion: Excisanin A is a potent HIF-1α inhibitor, supporting its potential development for human hepatoma therapy.
Keywords: Excisanin A, HIF-1α, Protein synthesis, Hepatoma therapy
(+)-Catechin Produces Antiproliferative Effects in Human Hepatocellular Carcinoma Cells and Inhibits Tumor Growth in Vivo
