N-acetyl cysteine and penicillamine induce apoptosis via the ER stress response-signaling pathway

✍ Scribed by Dongyin Guan; Yingying Xu; Min Yang; Hao Wang; Xiaoming Wang; Zonghou Shen

• Book ID: 102499329
• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 258 KB
• Volume: 49
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20578

✦ Synopsis

N-acetyl cysteine (NAC) and penicillamine (PEN) have been shown to induce apoptosis in multiple types of human cancer cells; however, the molecular mechanism underlying this activity is unclear. This study was designed to identify the genes responsible for apoptosis induction by NAC and PEN. We found that glucose-regulated protein 78 (GRP78) was upregulated in HeLa cells following treatment with NAC or PEN. GRP78 is a central regulator of endoplasmic reticulum (ER) stress and has been used as a marker of ER stress. Additionally, both the activating transcription factor 6 (ATF6) protein and X box-binding protein 1 (XBP1) mRNA were processed, which facilitates the expression of C/EBP homologous protein (CHOP), a key-signaling component of ER stress-induced apoptosis. Furthermore, the PERK-ATF4 pathway, which also induces the expression of CHOP, was activated in NAC-treated cells. The role of the ER stress pathway was further confirmed through the small interfering RNA (siRNA)-mediated knockdown of CHOP, which attenuated NAC and PEN-induced apoptosis. These results demonstrate that NAC-and PEN-induced apoptosis in HeLa cells is mediated by the ER stress pathway.