title: Over-expression of Smac promotes TRAIL-induced cell death in human hepatocellular carcinoma.
abstract: The second mitochondria-derived activator of caspase, Smac, is an apoptosis-related protein. Smac releases inhibition of the IAP family from caspase-3 to induce apoptosis. Smac is expressed in some malignant tumor cells and is released from mitochondria into the cytosol after death receptor stimulation to promote apoptosis of tumor cells. In this study, we found down-regulated Smac protein expression in hepatocellular carcinoma (HCC) tissues, compared to that in non-tumor hepatic tissues. Simultaneously, caspase-3 expression also decreased in HCC tissues. HCC cell lines did not undergo apoptosis after TRAIL stimulation, although Smac was expressed in these HCC cells. Ectopic Smac alone did not induce cell death, but could sensitize HCC cells to TRAIL stimulation. With over-expression of Smac in HCC cells, TRAIL induced by 10% HCC cell death. The role of Smac in apoptosis signaling pathway in HCC cells warrants further study.
authors.affiliation: First Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okano
authors.forename: Katsuya
authors.initials: K
authors.lastname: Shiraki
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Inoue
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawakita
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Saitou
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Enokimura
authors.forename: Norihiko
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Fujikawa
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Murata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D051017:Apoptosis Regulatory Proteins; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D016923:Cell Death; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008113:Liver Neoplasms / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha