Mechanisms involved in curcumin-induced human neutrophil apoptosis: Evidence that curcumin activates the endoplasmic reticulum stress-induced cell apoptosis pathway.

Curcumin was previously reported to accelerate neutrophil apoptosis, but the mechanism is unclear. Herein, we confirmed that curcumin induces human neutrophil apoptosis as assessed by cytology and by increase in the cell surface expression of annexin-V and CD16 shedding. Curcumin activated caspase-3 and the cleavage of the two cytoskeletal proteins lamin B1 and vimentin. In addition, curcumin activated protein kinase RNA-like endoplasmic reticulum kinase and eukaryotic initiation factor 2 alpha and reduced de novo protein synthesis and the protein expression of the two chaperone proteins, HSP70 and HSP90. We conclude that curcumin acts as an endoplasmic reticulum stressor in human neutrophils. The ability of curcumin to activate the endoplasmic reticulum stress-induced cell apoptotic pathway is part of its mode of action in primary cells like mature neutrophils.