salubrinal and Urinary-Bladder-Neoplasms

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 T24 cells. ER stress inhibitor salubrinal, or PERK silencing, diminishes ursolic acid-induced anti-T24 cell effects. Salubrinal inhibits ursolic acid-induced CHOP expression, Bim ER accumulation and caspase-3 activation in T24 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.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Bcl-2-Like Protein 11; Caspase 3; Cell Line, Tumor; Cinnamates; eIF-2 Kinase; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Endoribonucleases; Humans; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase Kinase 5; Membrane Proteins; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; RNA Interference; RNA, Small Interfering; Signal Transduction; Thiourea; TNF Receptor-Associated Factor 2; Transcription Factor CHOP; Triterpenes; Urinary Bladder Neoplasms; Ursolic Acid