title: Antiproliferation of Cryptocarya concinna-derived cryptocaryone against oral cancer cells involving apoptosis, oxidative stress, and DNA damage.
abstract: BACKGROUND
  Cryptocarya-derived crude extracts and their compounds have been reported to have an antiproliferation effect on several types of cancers but their impact on oral cancer is less well understood.
  
  
  METHODS
  We examined the cell proliferation effect and mechanism of C. concinna-derived cryptocaryone (CPC) on oral cancer cells in terms of cell viability, apoptosis, reactive oxygen species (ROS), mitochondrial depolarization, and DNA damage.
  
  
  RESULTS
  We found that CPC dose-responsively reduced cell viability of two types of oral cancer cells (Ca9-22 and CAL 27) in MTS assay. The CPC-induced dose-responsive apoptosis effects on Ca9-22 cells were confirmed by flow cytometry-based sub-G1 accumulation, annexin V staining, and pancaspase analyses. For oral cancer Ca9-22 cells, CPC also induced oxidative stress responses in terms of ROS generation and mitochondrial depolarization. Moreover, γH2AX flow cytometry showed DNA damage in CPC-treated Ca9-22 cells. CPC-induced cell responses in terms of cell viability, apoptosis, oxidative stress, and DNA damage were rescued by N-acetylcysteine pretreatment, suggesting that oxidative stress plays an important role in CPC-induced death of oral cancer cells.
  
  
  CONCLUSIONS
  CPC is a potential ROS-mediated natural product for anti-oral cancer therapy.
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. hschang@kmu.edu.tw.|School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. hschang@kmu.edu.tw.
authors.forename: Hsun-Shuo
authors.initials: HS
authors.lastname: Chang
authors.affiliation: 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.|Department of Radiation Oncology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan. reyata@kmu.edu.tw.
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Tang
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: 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 Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan. cywu@mail.nsysu.edu.tw.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. tpircsnart@gmail.com.
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Chung
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. whr0319@gmail.com.
authors.forename: Hui-Ru
authors.initials: HR
authors.lastname: Wang
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. m635013@kmu.edu.tw.|School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. m635013@kmu.edu.tw.
authors.forename: Ih-Sheng
authors.initials: IS
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. miyihu@gmail.com.|Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. miyihu@gmail.com.
authors.forename: Ming-Yii
authors.initials: MY
authors.lastname: Huang
authors.affiliation: 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.|Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. changhw@kmu.edu.tw.|Center for Reseach Resources and Development of Kaohsiung Medical University, Kaohsiung, 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*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D031369:Cryptocarya / Q000737:chemistry*; D004249:DNA Damage; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy*; D018384:Oxidative Stress; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011753:Pyrones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D011753:Pyrones; C548572:cryptocaryone