title: Curcumin induces pro-apoptotic endoplasmic reticulum stress in human leukemia HL-60 cells.
abstract: 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-2alpha, 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.
authors.affiliation: Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Hyun-Ock
authors.initials: HO
authors.lastname: Pae
authors.forename: Sun-Oh
authors.initials: SO
authors.lastname: Jeong
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
authors.forename: Ki Mo
authors.initials: KM
authors.lastname: Kim
authors.forename: Hak Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Soon-Ai
authors.initials: SA
authors.lastname: Kim
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Sung-Don
authors.initials: SD
authors.lastname: Kang
authors.forename: Byeong-Nam
authors.initials: BN
authors.lastname: Kim
authors.forename: Hun-Taeg
authors.initials: HT
authors.lastname: Chung
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D061945:Caspase Inhibitors; D053471:Caspases, Initiator / Q000378:metabolism; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D034741:RNA, Small Interfering / Q000235:genetics; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; C497249:DDIT3 protein, human; D034741:RNA, Small Interfering; C096277:tetrahydrocurcumin; D051742:Transcription Factor CHOP; C093516:CASP4 protein, human; D053471:Caspases, Initiator; D003474:Curcumin