title: Targeting cancer cells via the reactive oxygen species-mediated unfolded protein response with a novel synthetic polyphenol conjugate.
abstract: OBJECTIVE
  The selective killing of tumor cells is an important strategy for cancer therapeutics. The aim of this study was to develop a novel antitumor agent that is safe for normal cells with the ability to selectively target cancer cells.
  
  
  METHODS
  On the basis of quantitative structure-activity relationship, we synthesized a novel polyphenol conjugate (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (DPP-23). We evaluated the effect of DPP-23 on proliferation, cell cycle, and apoptosis in various tumor cells. We also assessed molecular targets of DPP-23 using genome-wide expression profiling by DNA microarray and real-time PCR array systems.
  
  
  RESULTS
  DPP-23 effectively inhibited the growth of cancer cells in vitro and in vivo (xenografts in Balb/c nude mice). At a molecular level, DPP-23 targeted the unfolded protein response (UPR) in the endoplasmic reticulum (ER) through the production of reactive oxygen species (ROS) in cancer cells, but not in normal cells, resulting in selective killing of tumor cells via caspase-dependent apoptosis.
  
  
  CONCLUSIONS
  The selective generation of ROS in cancer cells could be an attractive strategy for the selective killing of cancer cells, while maintaining negligible cytotoxicity to normal cells. DPP-23 represents a promising novel therapeutic agent for the selective production of ROS in cancer cells.
authors.affiliation: Department of Biological Sciences, College of Biological Science and Biotechnology, and Cancer and Metabolism Institute, Konkuk University, Seoul, Republic of Korea.
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Shin
authors.affiliation: Department of Biological Sciences, College of Biological Science and Biotechnology, and.
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, College of Biological Science and Biotechnology, and.
authors.forename: Mi So
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Applied Chemistry, Dongduk Women's University, Seoul, Republic of Korea.
authors.forename: Dongsoo
authors.initials: D
authors.lastname: Koh
authors.affiliation: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul, Republic of Korea.
authors.forename: Hyeryoung
authors.initials: H
authors.lastname: Jung
authors.affiliation: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul, Republic of Korea. yhlee58@konkuk.ac.kr yoongho@konkuk.ac.kr.
authors.forename: Yoongho
authors.initials: Y
authors.lastname: Lim
authors.affiliation: Department of Biological Sciences, College of Biological Science and Biotechnology, and Cancer and Metabolism Institute, Konkuk University, Seoul, Republic of Korea. yhlee58@konkuk.ac.kr yoongho@konkuk.ac.kr.
authors.forename: Young Han
authors.initials: YH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D056811:Unfolded Protein Response / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: C000601997:3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one; D000970:Antineoplastic Agents; D047188:Chalcones; D059808:Polyphenols; D012333:RNA, Messenger; D017382:Reactive Oxygen Species