title: Concentration effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis, oxidative stress, and DNA damage.
abstract: BACKGROUND
  Grape seeds extract (GSE) is a famous health food supplement for its antioxidant property. Different concentrations of GSE may have different impacts on cellular oxidative/reduction homeostasis. Antiproliferative effect of GSE has been reported in many cancers but rarely in oral cancer.
  
  
  METHODS
  The aim of this study is to examine the antioral cancer effects of different concentrations of GSE in terms of cell viability, apoptosis, reactive oxygen species (ROS), mitochondrial function, and DNA damage.
  
  
  RESULTS
  High concentrations (50-400 μg/ml) of GSE dose-responsively inhibited proliferation of oral cancer Ca9-22 cells but low concentrations (1-10 μg/ml) of GSE showed a mild effect in a MTS assay. For apoptosis analyses, subG1 population and annexin V intensity in high concentrations of GSE-treated Ca9-22 cells was increased but less so at low concentrations. ROS generation and mitochondrial depolarization increased dose-responsively at high concentrations but showed minor changes at low concentrations of GSE in Ca9-22 cells. Additionally, high concentrations of GSE dose-responsively induced more γH2AX-based DNA damage than low concentrations.
  
  
  CONCLUSIONS
  Differential concentrations of GSE may have a differentially antiproliferative function against oral cancer cells via differential apoptosis, oxidative stress and DNA damage.
authors.affiliation: Department of Oral and Maxillofacial Surgery Chi-Mei Medical Center, Tainan, Taiwan. ycysmc@yahoo.com.tw.|School of Dentistry, Taipei Medical University, Taipei, Taiwan. ycysmc@yahoo.com.tw.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Yen
authors.affiliation: Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. mifeho@kmu.edu.tw.|Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. mifeho@kmu.edu.tw.|Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan. mifeho@kmu.edu.tw.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan. sppom@hotmail.com.
authors.forename: Zhi-Wen
authors.initials: ZW
authors.lastname: Yang
authors.affiliation: Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. reyata@kmu.edu.tw.|Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. reyata@kmu.edu.tw.|Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. reyata@kmu.edu.tw.
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Tang
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. sherry30126@yahoo.com.tw.
authors.forename: Kun-Tzu
authors.initials: KT
authors.lastname: Li
authors.affiliation: Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. sting@mail.nsysu.edu.tw.
authors.forename: Hurng-Wern
authors.initials: HW
authors.lastname: Huang
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan. emily20100908@hotmail.com.tw.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Huang
authors.affiliation: School of Dentistry and Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan. seanlee@tmu.edu.tw.
authors.forename: Sheng-Yang
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, School of Medicine, National Cheng Kung University, Tainan, Taiwan. tffu@mail.ncku.edu.tw.
authors.forename: Tzu-Fun
authors.initials: TF
authors.lastname: Fu
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. ken36547@gmail.com.
authors.forename: Che-Yu
authors.initials: CY
authors.lastname: Hsieh
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan. bhchen@kmu.edu.tw.
authors.forename: Bing-Hung
authors.initials: BH
authors.lastname: Chen
authors.affiliation: Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. changhw@kmu.edu.tw.|Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. changhw@kmu.edu.tw.|Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan. changhw@kmu.edu.tw.|Research Center of Environmental Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. changhw@kmu.edu.tw.
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D056604:Grape Seed Extract / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D017382:Reactive Oxygen Species; D012639:Seeds; D027843:Vitis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D056604:Grape Seed Extract; D017382:Reactive Oxygen Species