title: Tetrandrine induces programmed cell death in human oral cancer CAL 27 cells through the reactive oxygen species production and caspase-dependent pathways and associated with beclin-1-induced cell autophagy.
abstract: Tetrandrine, a bisbenzylisoquinoline alkaloid, is extracted from the root of the Chinese herb Radix Stephania tetrandra S Moore. This compound has antitumor activity in different cancer cell types. In this study, the effects of tetrandrine on human oral cancer CAL 27 cells were examined. Results indicated that tetrandrine induced cytotoxic activity in CAL 27 cells. Effects were due to cell death by the induction of apoptosis and accompany with autophagy and these effects were concentration- and time-dependent manners. Tetrandrine induced apoptosis was accompanied by alterations in cell morphology, chromatin fragmentation, and caspase activation in CAL 27 cells. Tetrandrine treatment also induced intracellular accumulation of reactive oxygen species (ROS). The generation of ROS may play an important role in tetrandrine-induced apoptosis. Tetrandrine triggered LC3B expression and induced autophagy in CAL 27 cells. Tetrandrine induced apoptosis and autophagy were significantly attenuated by N-acetylcysteine pretreatment that supports the involvement of ROS production. Tetrandrine induced cell death may act through caspase-dependent apoptosis with Beclin-1-induced autophagy in human oral cancer cells. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 329-343, 2017.
authors.affiliation: Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, 404, Taiwan.
authors.forename: Jin-Cherng
authors.initials: JC
authors.lastname: Lien
authors.affiliation: Department of Nursing, Cardinal Tien Junior College of Healthcare and Management, New Taipei, 231, Taiwan.
authors.forename: Meng-Wei
authors.initials: MW
authors.lastname: Lin
authors.affiliation: School of Pharmacy, China Medical University, Taichung, 404, Taiwan.
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chang
authors.affiliation: Department of Surgery, China Medical University Beigang Hospital, Yunlin, 651, Taiwan.|School of Medicine, China Medical University Hospital, Taichung, 404, Taiwan.
authors.forename: Kuang-Chi
authors.initials: KC
authors.lastname: Lai
authors.affiliation: Department of Nursing, St. Mary's Medicine Nursing and Management College, Yilan, 266, Taiwan.
authors.forename: An-Cheng
authors.initials: AC
authors.lastname: Huang
authors.affiliation: Department of Dentist, China Medical University, Taichung, 404, Taiwan.
authors.forename: Fu-Shun
authors.initials: FS
authors.lastname: Yu
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.|Department of Biotechnology, Asia University, Taichung, 413, Taiwan.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000378:metabolism*; D044182:Benzylisoquinolines / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D044182:Benzylisoquinolines; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; C009438:tetrandrine; D020169:Caspases; D002118:Calcium; D000111:Acetylcysteine
keywords: CAL 27 cell line; apoptosis; autophagy; oral cancer; tetrandrine