Curcumin induces pro-apoptotic endoplasmic reticulum stress in human leukemia HL-60 cells

• Published in: Biochemical and biophysical research communications 2007-02, Vol.353 (4), p.1040-1045
• Main Authors: Pae, Hyun-Ock, Jeong, Sun-Oh, Jeong, Gil-Saeng, Kim, Ki Mo, Kim, Hak Sung, Kim, Soon-Ai, Kim, Youn-Chul, Kang, Sung-Don, Kim, Byeong-Nam, Chung, Hun-Taeg
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Blotting, Western; Caspase Inhibitors; Caspases, Initiator - metabolism; Curcumin; Curcumin - analogs & derivatives; Curcumin - chemistry; Curcumin - pharmacology; Dose-Response Relationship, Drug; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Endoplasmic reticulum stress; HL-60 Cells; Humans; Leukemia, Promyelocytic, Acute - genetics; Leukemia, Promyelocytic, Acute - metabolism; Leukemia, Promyelocytic, Acute - pathology; Molecular Structure; RNA, Small Interfering - genetics; Tetrahydrocurcumin; Transcription Factor CHOP - genetics; Transcription Factor CHOP - metabolism; Transfection; Unfolded protein response
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.12.133

Curcumin has been shown to induce apoptosis in many cancer cells. However, the molecular mechanism(s) responsible for curcumin-induced apoptosis is not well understood and most probably involves several pathways. In HL-60 cells, curcumin induced apoptosis and endoplasmic reticulum (ER) stress as evidenced by the survival molecules such as phosphorylated protein kinase-like ER-resident kinase, phosphorylated eukaryotic initiation factor-2α, glucose-regulated protein-78, and the apoptotic molecules such as caspase-4 and CAAT/enhancer binding protein homologous protein (CHOP). Inhibition of caspase-4 activity by z-LEVD-FMK, blockage of CHOP expression by small interfering RNA, and treatment with salubrinal, an ER inhibitor, significantly reduced curcumin-induced apoptosis. Removing two double bonds in curcumin, which was speculated to form Michael adducts with thiols in secretory proteins, resulted in a loss of the ability of curcumin to induce apoptosis as well as ER stress. Thus, the present study shows that curcumin-induced apoptosis is associated with its ability to cause ER stress.