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

Abstract

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.