title: Tetrandrine Induces Apoptosis of Human Nasopharyngeal Carcinoma NPC-TW 076 Cells through Reactive Oxygen Species Accompanied by an Endoplasmic Reticulum Stress Signaling Pathway.
abstract: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy of the head and neck and the incidence is higher in Southeast Asia. Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid, a natural product, and exhibits biological activities including action against many human cancer cell lines. However, the molecular mechanism of TET-induced cell apoptosis in human NPC cells is still unclear. In the present study, we investigated TET-induced apoptotic cell death and associated possible signal pathways on human nasopharyngeal carcinoma NPC-TW 076 cells in vitro. Phase contrast microscopy was used to examine cell morphology and DAPI staining was used to examine chromatin condensation. Flow cytometry assay was used to measure total viable cells, cell cycle and sub-G₁ phase distribution, reactive oxygen species (ROS), Ca2+, and mitochondria membrane potential (ΔΨm) in NPC-TW 076 cells. Results indicate that TET induced cell death through the cell morphological changes, caused G₀/G₁ phase arrest, increased ROS and Ca2+production, and finally caused apoptotic cell death in NPC-TW 076 cells. There was no influence on the level of ΔΨmafter TET treatment. Western blotting indicated that TET increased endoplasmic reticulum (ER) stress associated protein expression such as GADD153, GRP78, ATF-6α and ATF-6 βwhich indicated that TET induced cell death through ER stress. ER stress is a potential target in cancer treatment, so the ability of TET to induce ER stress response and to activate programming cell death in NPC-TW 076 cells make this molecule become a promising anticancer agent.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan. cathy263938@gmail.com.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan. sfpeng@mail.cmu.edu.tw.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Peng
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan. mllinsally@yahoo.com.tw.
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Lin
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan. clkuo@mail.cmu.edu.tw.
authors.forename: Chao-Lin
authors.initials: CL
authors.lastname: Kuo
authors.affiliation: College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 40402, Taiwan. prorna@mail.cmu.edu.tw.
authors.forename: Kung-Wen
authors.initials: KW
authors.lastname: Lu
authors.affiliation: College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 40402, Taiwan. qbking@ms29.hinet.net.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Liao
authors.affiliation: Department of Chinese Medicine, E-Da Hospital, Kaohsiung 82445, Taiwan. m2367591@ms25.hinet.net.|School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 82445, Taiwan. m2367591@ms25.hinet.net.
authors.forename: Yi-Shih
authors.initials: YS
authors.lastname: Ma
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Wufeng, Taichung 41354, Taiwan. fushin@asia.edu.tw.
authors.forename: Fu-Shin
authors.initials: FS
authors.lastname: Chueh
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan. kchliu@mail.cmu.edu.tw.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Liu
authors.affiliation: School of Dentistry, China Medical University, Taichung 40402, Taiwan. fsyu@mail.cmu.edu.tw.
authors.forename: Fu-Shun
authors.initials: FS
authors.lastname: Yu
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan. jgchung@mail.cmu.edu.tw.|Department of Biotechnology, Asia University, Wufeng, Taichung 41354, Taiwan. jgchung@mail.cmu.edu.tw.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002277:Carcinoma; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D017382:Reactive Oxygen Species; C009438:tetrandrine
keywords: NPC-TW 076 cells; apoptosis; endoplasmic reticulum (ER) stress; reactive oxygen species (ROS); tetrandrine (TET)