title: Endoplasmic reticulum stress mediates the arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells.
abstract: Arsenic trioxide has been proven to trigger apoptosis in human hepatocellular carcinoma cells. Endoplasmic reticulum stress has been known to be involved in apoptosis through the induction of CCAAT/enhancer-binding protein homologous protein. However, it is unknown whether endoplasmic reticulum stress mediates arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells. Our data showed that arsenic trioxide significantly induced apoptosis in human hepatocellular carcinoma cells. Furthermore, arsenic trioxide triggered endoplasmic reticulum stress, as indicated by endoplasmic reticulum dilation, upregulation of glucose-regulated protein 78 and CCAAT/enhancer-binding protein homologous protein. We further found that 4-phenylbutyric acid, an inhibitor of endoplasmic reticulum stress, alleviated arsenic trioxide-induced expression of CCAAT/enhancer-binding protein homologous protein. More important, knockdown of CCAAT/enhancer-binding protein homologous protein by siRNA or inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid alleviated apoptosis induced by arsenic trioxide. Consequently, our results suggested that arsenic trioxide could induce endoplasmic reticulum stress-mediated apoptosis in hepatocellular carcinoma cells, and that CCAAT/enhancer-binding protein homologous protein might play an important role in this process.
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China; Department of Outpatient Surgery, Linyi People's Hospital, Linyi, Shandong 276000, China.
authors.forename: Shu-Meng
authors.initials: SM
authors.lastname: Yang
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China; Department of Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Hao-Peng
authors.initials: HP
authors.lastname: Zhang
authors.affiliation: Cancer Research Institute, Harbin Medical University, Harbin 150081, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Shi-Bo
authors.initials: SB
authors.lastname: Sun
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China; Department of Surgery, The Fourth People's Hospital of Linfen, Shanxi 041000, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Chang
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Xuan-Chen
authors.initials: XC
authors.lastname: Tao
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors.forename: Tuo-Yun
authors.initials: TY
authors.lastname: Yang
authors.affiliation: The Assisted Reproduction Department, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China. Electronic address: yangym0916@163.com.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D010087:Oxides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010654:Phenylbutyrates / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D001152:Arsenicals; D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D010087:Oxides; D010654:Phenylbutyrates; D034741:RNA, Small Interfering; D051742:Transcription Factor CHOP; C075773:4-phenylbutyric acid; D000077237:Arsenic Trioxide
keywords: Apoptosis; Arsenic trioxide; CCAAT/enhancer-binding protein homologous protein; Endoplasmic reticulum stress; Hepatocellular carcinoma cells