Endoplasmic reticulum stress contributes to arsenic trioxide-induced apoptosis in drug-sensitive and -resistant leukemia cells

Abstract

This study characterized the role of endoplasmic reticulum stress (ERS)-related pathways in arsenic trioxide-induced apoptosis in multidrug-resistant leukemia K562/ADM cells. Arsenic trioxide exposure led to much significant induction of apoptosis in K562/ADM cells than the parental K562 cells, and the chaperone proteins glucose-regulated protein 78, CHOP/GADD153, X-box binding protein-1 and caspase-12 were activated to varying degrees. Furthermore, arsenic trioxide stimulation led to inhibition of P-glycoprotein and Bcl-2 expression. This study demonstrates a missing link between arsenic trioxide and ERS-induced apoptosis, and suggests that the greater effects obtained in drug-resistant K562/ADM cells may be mediated by downregulation of P-glycoprotein and Bcl-2 expression.