title: Sinuleptolide inhibits proliferation of oral cancer Ca9-22 cells involving apoptosis, oxidative stress, and DNA damage.
abstract: OBJECTIVE
  Sinuleptolide, a soft corals-derived bioactive norditerpenoid, is a marine natural product with a potent anti-inflammatory effect. We evaluate the potential anti-oral cancer effects of sinuleptolide and investigate the possible mechanisms involved.
  
  
  METHODS
  Cell viability, cell cycle, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and DNA damage analyses were performed.
  
  
  RESULTS
  In a cell viability assay, we found that sinuleptolide is dose-responsively antiproliferative against oral gingival cancer Ca9-22 cells but less harmful to normal human gingival fibroblast (HGF-1) cells (P<0.001). In cell cycle analysis, sinuleptolide induced subG1 accumulation at a higher dose and led to G2/M arrest of Ca9-22 cells (P<0.005). Apoptosis was significantly increased in sinuleptolide-treated Ca9-22 cells based on annexin V and poly(ADP-ribose) polymerase (PARP) expressions (P<0.05-0.0001). Based on flow cytometer analysis, sinuleptolide also induced the generation of ROS and decreased MMP in a dose-responsive manner (P<0.05-0.0001). DNA damage increased dose-responsively after sinuleptolide treatments (P < 0.001) based on comet and γH2AX assays.
  
  
  CONCLUSIONS
  Sinuleptolide can induce an antiproliferation of oral cancer Ca9-22 cells involving apoptosis, oxidative stress and DNA damage, suggesting that sinuleptolide represents a potential chemotherapeutic drug for oral cancer treatment.
authors.affiliation: Doctor Degree Program in Marine Biotechnology, National Sun Yat-sen University/Academia Sinica, Kaohsiung 80424, Taiwan. Electronic address: poppiiyy@gmail.com.
authors.forename: Yung-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. Electronic address: betty8575@yahoo.com.tw.
authors.forename: Chiung-Yao
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: sherry30126@yahoo.com.tw.
authors.forename: Kun-Tzu
authors.initials: KT
authors.lastname: Li
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: runili@kmu.edu.tw.
authors.forename: Ruei-Nian
authors.initials: RN
authors.lastname: Li
authors.affiliation: Doctor Degree Program in Marine Biotechnology, National Sun Yat-sen University/Academia Sinica, Kaohsiung 80424, Taiwan; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. Electronic address: ccliaw@mail.nsysu.edu.tw.
authors.forename: Chih-Chuang
authors.initials: CC
authors.lastname: Liaw
authors.affiliation: Doctor Degree Program in Marine Biotechnology, National Sun Yat-sen University/Academia Sinica, Kaohsiung 80424, Taiwan; Institute of Biological Chemistry, Academia Sinica, Taipei 11524, Taiwan. Electronic address: shwu@gate.sinica.edu.tw.
authors.forename: Shih-Hsiung
authors.initials: SH
authors.lastname: Wu
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: clumyfish2006@gmail.com.
authors.forename: Jing-Ru
authors.initials: JR
authors.lastname: Liu
authors.affiliation: Doctor Degree Program in Marine Biotechnology, National Sun Yat-sen University/Academia Sinica, Kaohsiung 80424, Taiwan; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan. Electronic address: sheu@mail.nsysu.edu.tw.
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Sheu
authors.affiliation: Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Center for Research Resources and Development of Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: changhw@kmu.edu.tw.
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006657:Histones / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004224:Diterpenes; C468783:H2AX protein, human; D006657:Histones; D017382:Reactive Oxygen Species; C477928:sinuleptolide; D011065:Poly(ADP-ribose) Polymerases
keywords: Apoptosis; DNA damage; Mitochondrial membrane potential; Oral cancer; Sinuleptolide; Soft corals