title: Ulmus davidiana Nakai induces apoptosis and autophagy on non-small cell lung cancer cells.
abstract: BACKGROUND
  Ulmus davidiana Nakai (UDN) is frequently used in the treatment of cancer in traditional oriental medicine. Although several reports indicate that UDN has inhibitory effects in some cancers, there has been no report on the inhibitory effects of UDN via both autophagy and apoptosis.
  
  
  METHODS
  Cytotoxicity induced by UDN in human non-small cell lung cancer (NSCLC) H-1299 and H-460 cell lines was evaluated using the 2, 3-Bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) assay and trypan blue exclusion assay. Induction of apoptosis was also investigated using Hoechst staining and annexin-V binding assay and was confirmed with western blot analysis. Induction of autophagy was investigated through observation of autophagy vacuoles under inverted phase-contrast microscopy and was confirmed by observing the formation of autophagy vacuoles under a fluorescence microscope using monodansylcadaverine (MDC) staining and western blot analysis. The in vivo anti-tumorigenic effect of UDN was investigated in an athymic nude mouse xenograft model using H-1299 NSCLC cells.
  
  
  RESULTS
  UDN exhibited a marked inhibitory effect on cell growth in H-1299 and H-460 human NSCLC cell lines in a dose- and time-dependent manner in vitro and in vivo. It induced not only apoptosis, but also autophagy in both H-1299 and H-460 cells in a dose-dependent manner. UDN-mediated autophagy led to the accumulation of autophagosome, resulting in apoptosis induction and cell death.
  
  
  CONCLUSIONS
  From our current knowledge, we are the first to demonstrate that UDN has the potential to induce both autophagy and apoptosis in H-1299 and H-460 human NSCLC cell lines. We suggest that UDN can be considered a potential candidate for lung cancer-specific chemotherapy with efficacy as a cytotoxic agent.
authors.affiliation: Department of Biomedical Sciences, Korea University College of Medicine, Seoul 136-705, Republic of Korea; Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 136-705, Republic of Korea.
authors.forename: Soon-Oh
authors.initials: SO
authors.lastname: Hong
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, Korea University Medical Center, Seoul 136-705, Republic of Korea.
authors.forename: In Keun
authors.initials: IK
authors.lastname: Choi
authors.affiliation: Bio-Center, Gyeonggido Business & Science Accelerator, Suwon 16229, Republic of Korea.
authors.forename: Wonsik
authors.initials: W
authors.lastname: Jeong
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, Korea University Medical Center, Seoul 136-705, Republic of Korea.
authors.forename: Se Ryeon
authors.initials: SR
authors.lastname: Lee
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, Korea University Medical Center, Seoul 136-705, Republic of Korea.
authors.forename: Hwa Jung
authors.initials: HJ
authors.lastname: Sung
authors.affiliation: Bio-Center, Gyeonggido Business & Science Accelerator, Suwon 16229, Republic of Korea.
authors.forename: Seong Su
authors.initials: SS
authors.lastname: Hong
authors.affiliation: Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 136-705, Republic of Korea; Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703, Republic of Korea. Electronic address: cancer@korea.ac.kr.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Seo
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000494:pharmacology; D034403:Ulmus / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering
keywords: Apoptosis; Autophagy; Autophagy flux; Autophagy inhibitor; H-1299 and H-460 human non-small cell lung cancer cell lines; Ulmus davidiana Nakai (UDN)