title: Emodin induces apoptosis of lung cancer cells through ER stress and the TRIB3/NF-κB pathway.
abstract: Emodin is a phytochemical with potent anticancer activities against various human malignant cancer types, including lung cancer; however, the molecular mechanisms underlying the effects of emodin remain unclear. In the present study, the A549 and H1299 human non-small lung cancer cell lines were treated with emodin and the induced molecular effects were investigated. Changes in cell viability were evaluated by MTT assay, Hoechst staining was used to indicate the apoptotic cells, and western blotting was utilized to assess endoplasmic reticulum (ER) stress and signaling changes. RNA interference was also employed to further examine the role of tribbles homolog 3 (TRIB3) in the emodin-induced apoptosis of lung cancer cells. Emodin was found to reduce the viability of lung cancer cells and induce apoptosis in a concentration-dependent manner. Emodin-induced apoptosis was impaired by inhibition of ER stress using 4-phenylbutyrate (4-PBA). ER stress and TRIB3/nuclear factor-κB signaling was activated in emodin-treated lung cancer cells. Emodin-induced apoptosis was reduced by TRIB3 knockdown in A549 cells, whereas ER stress was not reduced. In vivo assays verified the significance of these results, revealing that emodin inhibited lung cancer growth and that the inhibitory effects were reduced by inhibition of ER stress with 4-PBA. In conclusion, the results suggest that TRIB3 signaling is associated with emodin-induced ER stress-mediated apoptosis in lung cancer cells.
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Su
authors.affiliation: The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
authors.forename: Jingkun
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Surgery, Xi'an Feng Cheng Hospital, Xi'an, Shaanxi, P.R. China.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Radiotherapy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Vascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004642:Emodin / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D018797:Cell Cycle Proteins; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D017346:Protein Serine-Threonine Kinases; D004642:Emodin