Hyperoside induces cell cycle arrest and suppresses tumorigenesis in bladder cancer through the interaction of EGFR-Ras and Fas signaling pathways

Abstract

Abstract Background Hyperoside is a natural flavonol glycoside widely found in plants and has been reported to have a variety of pharmacological effects, including anticancer abilities. However, the antitumor effect of hyperoside on bladder cancer has not been studied, and its exact mechanism and targets remain unclear. Methods The human bladder cancer cells T24 and 5637 were treated by hyperoside and evaluated by MTT assay and flow cytometry. The underlying mechanisms were investigated by quantitative proteomics and bioinformatics analyses. The variation of proteins was confirmed by Western blot. In vivo studies were conducted using tumor-bearing mice to evaluate the anti-tumor effects of hyperoside in bladder cancer. Results We demonstrated for the first time that hyperoside repressed the proliferation of bladder cancer cells in vitro and in vivo. Moreover, hyperoside could not only induce cell cycle arrest, but also cause apoptosis of a few bladder cancer cells. Specifically, hyperoside induced overexpression of EGFR, Ras and Fas proteins, which affects a variety of synergistic and antagonistic downstream signaling pathways, including MAPKs and Akt, ultimately contributing to its anticancer effects in bladder cancer cells. Conclusions This study reveals that hyperoside could be a promising therapeutic strategy for the prevention of bladder cancer.