Suppression effects of O-demethyldemethoxycurcumin on thapsigargin triggered on endoplasmic reticulum stress in SK-N-SH cells

• O-demethyldemethoxycurcumin protects the SK-N-SH cells from thapsigargin-induced neurotoxicity.
• O-demethyldemethoxycurcumin protects the SK-N-SH cells during ER stress through the suppression of CHOP expression by inhibiting PERK, IRE1 and ATF6 pathways.
• O-demethyldemethoxycurcumin effectively inhibits thapsigargin-induced apoptosis associated with ER stress in neuronal cells.

Endoplasmic reticulum (ER) stress is involved in neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Therefore, interventions that attenuate ER stress may contribute to induction in apoptotic cell death. This study aimed to evaluate the potential involvement of O-demethyldemethoxycurcumin, an analog of curcuminoids, on thapsigargin-induced apoptosis in cultured neuroblastoma (SK-N-SH) cells through the ER stress signaling pathway. The results showed that O-demethyldemethoxycurcumin reduced thapsigargin induced cell death in SK-N-SH cells and the release of lactate dehydrogenase (LDH) by decreasing the apoptotic cell death induced by thapsigargin. Consistent with these findings, O-demethyldemethoxycurcumin inhibited the thapsigargin-induced activation of cleavagecaspase-12. Moreover, O-demethyldemethoxycurcumin attenuated the intracellular Ca2+ level and the expression of the calpain protein. O-demethyldemethoxycurcumin also downregulated the expression of ER stress signaling proteins, including the phosphorylation of PKR-like endoplasmic reticulum kinase (p-PERK), the phosphorylation of inositol-requiring enzyme 1 (p-IRE1), activating transcription factor 6 (ATF6), binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP). Our findings suggest that O-demethyldemethoxycurcumin could protect against thapsigargin-induced ER stress in SK-N-SH cells.