The Antitumor Activity of Pseudoginsengenin DQ Against Hypopharyngeal Cancer Cells via Targeting HIF-1α-GLUT1 Pathway

Abstract Background The ginsenosides have been reported to possess a variety of biological activities. Synthesized from the ginsenoside Protopanaxadiol (PPD), the octanone Pseudoginsengenin DQ (PDQ) may have stronger pharmacological effects as a secondary ginsenoside. Nevertheless, its antitumor activity and molecular mechanism against hypopharyngeal cancer cells remains unclear. Methods Cell Counting Kit-8, cell cycle assay and cell apoptosis assay were conducted to detect FADU cells proliferation, cell phase and apoptosis. The interactions between PDQ and HIF-1α were investigated by a molecular docking study. The expression of HIF-1α, GLUT1, apoptosis related proteins was tested by western blotting, direct stochastic optical reconstruction microscopy (dSTORM) and qRT-PCR. Glucose uptake assay was used to assess the glucose uptake capacity of FADU cells. Results PDQ was found to suppress the proliferation, reduce glucose uptake, induce the cell cycle arrest and apoptosis of FaDu cells. Molecular docking study demonstrated that PDQ could interact with the active site of HIF-1α. PDQ decreased the expression and mRNA levels of HIF-1α and its downstream factor GLUT1. Moreover, dSTORM results showed that PDQ reduced GLUT1 expression on the cell membrane but also inhibited its clustering. Conclusion Our work elucidated that the antitumor effect of PDQ is related to its downregulation of HIF-1α-GLUT1 pathway, suggesting that PDQ could be a potential therapeutic agent for hypopharyngeal cancer treatment.