Pseudoginsengenin DQ exerts antitumour activity against hypopharyngeal cancer cells by targeting the HIF-1α-GLUT1 pathway

Abstract

Background: Ginsenosides have been reported to possess a variety of biological activities. Synthesized from the ginsenoside protopanaxadiol (PPD), the octanone pseudoginsengenin DQ (PDQ) may have robust pharmacological effects as a secondary ginsenoside. Nevertheless, its antitumour activity and molecular mechanism against hypopharyngeal cancer cells remain unclear. Methods: Cell Counting Kit8 assays, cell cycle assays and cell apoptosis assays were conducted to assess FaDu cell 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, and apoptosis-related proteins was detected by Western blotting, direct stochastic optical reconstruction microscopy (dSTORM) and qRT-PCR. A glucose uptake assay was used to assess the glucose uptake capacity of FaDu cells. Results: PDQ suppressed proliferation, reduced glucose uptake, and induced cell cycle arrest and apoptosis in FaDu cells. A 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, the dSTORM results showed that PDQ reduced GLUT1 expression on the cell membrane and inhibited GLUT1 clustering. Conclusion: Our work showed that the antitumour effect of PDQ was related to the downregulation of the HIF-1α-GLUT1 pathway, suggesting that PDQ could be a potential therapeutic agent for hypopharyngeal cancer treatment.