Open AccessExcisanin A suppresses proliferation by inhibiting hypoxiainducible factor-1α expression in human hepatocellular carcinoma cells
Author(s) -
Li Han,
Changgao Jiang,
Chunliu Mi,
Ke Si Wang,
Hong Xiang Zuo,
Zhe Wang,
Ming Yue Li,
Zhi Hong Zhang,
Xuejun Jin
Publication year - 2021
Publication title -
tropical journal of pharmaceutical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.209
H-Index - 36
eISSN - 1596-5996
pISSN - 1596-9827
DOI - 10.4314/tjpr.v19i12.1
Subject(s) - clonogenic assay , hepatocellular carcinoma , microbiology and biotechnology , flow cytometry , chemistry , western blot , cell growth , messenger rna , cancer research , mtt assay , biology , in vitro , biochemistry , gene
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