Abstract
Chrysin is a natural flavone that has various biological activities, including antitumor effects. However, the effect of chrysin on bladder cancer cells remains elusive. The present study investigated the effects of chrysin on bladder cancer cells and its underlying mechanisms. The results demonstrated that chrysin induced apoptosis via the intrinsic pathway, as evidenced by activation of caspase-9 and caspase-3, however not caspase-8. In addition, chrysin reduced the expression of anti-apoptotic B cell lymphoma (Bcl) proteins including Bcl-2, Mcl-1, Bcl-xl, and promoted the protein expression of pro-apoptotic Bcl-2 associated X, apoptosis regulator. Chrysin also induced endoplasmic reticulum stress via activation of the unfolded protein response of PRKR-like endoplasmic reticulum kinase, eIF2α and activating transcription factor 4 in bladder cancer cells. Additionally, chrysin inhibited the signal transducer and activator of transcription 3 pathway. Furthermore, the generation of reactive oxygen species (ROS) was detected following treatment with chrysin. The ROS scavenger N-acetylcysteine inhibited the antitumor effect of chrysin. Collectively, these results indicate chrysin may act as a promising therapeutic candidate for targeting bladder cancer.