Ursolic acid induces ER stress response to activate ASK1-JNK signaling and induce apoptosis in human bladder cancer T24 cells

Here we studied the cellular mechanisms of ursolic acid's anti-bladder cancer ability by focusing on endoplasmic reticulum stress (ER stress) signaling. We show that ursolic acid induces a significant ER stress response in cultured human bladder cancer 124 cells. ER stress inhibitor salubrinal, or PERK silencing, diminishes ursolic acid-induced anti-T24 cell effects. Salubrinal inhibits ursolic add-induced CHOP expression, Bim ER accumulation and caspase-3 activation in 124 cells. Ursolic acid induces IRE1-TRAF2-ASK1 signaling complex formation to activate pro-apoptotic ASK1-JNK signaling. We suggest that ER stress contributes to ursolic acid's effects against bladder cancer cells. (C) 2012 Elsevier Inc. All rights reserved.