Yung-Ting Chang1, Chiung-Yao Huang2, Kun-Tzu Li3, Ruei-Nian Li4, Chih-Chuang Liaw5, Shih-Hsiung Wu6, Jing-Ru Liu7, Jyh-Horng Sheu8, Hsueh-Wei Chang9. 1. Doctor Degree Program in Marine Biotechnology, National Sun Yat-sen University/Academia Sinica, Kaohsiung 80424, Taiwan. Electronic address: poppiiyy@gmail.com. 2. Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. Electronic address: betty8575@yahoo.com.tw. 3. Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: sherry30126@yahoo.com.tw. 4. Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: runili@kmu.edu.tw. 5. 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. 6. 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. 7. Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address: clumyfish2006@gmail.com. 8. 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. 9. 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.
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. DESIGNS: 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. CONCLUSION: 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.
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. DESIGNS: 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. CONCLUSION: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: Elva Morretta; Roberta Esposito; Carmen Festa; Raffaele Riccio; Agostino Casapullo; Maria Chiara Monti Journal: Mar Drugs Date: 2017-10-13 Impact factor: 5.118