title: Reactive oxygen species-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to polydatin-induced apoptosis in human nasopharyngeal carcinoma CNE cells.
abstract: Previous studies revealed that polydatin, a natural small compound, possessed protective effect against ischemia/reperfusion injury and inflammation. However, the action and molecular mechanism of its potent anti-cancer activity remain poorly understood. In the present study, polydatin significantly killed several human tumor cell lines in a dose- and time-dependent manner. The compound also dose-dependently caused mitochondrial apoptosis in human nasopharyngeal carcinoma CNE cells. In addition, polydatin triggered endoplasmic reticulum (ER) stress and down-regulated the phosphorylation of Akt in CNE cells, while knock-down of CCAAT/enhancer-binding protein homologous protein (CHOP) dramatically abrogated the inactivation of Akt and reversed the pro-apoptotic effect of polydatin. Furthermore, polydatin provoked the generation of reactive oxygen species in CNE cells, while the antioxidant N-acetyl cysteine almost completely blocked the activation of ER stress and apoptosis, suggesting polydatin-induced reactive oxygen species is an early event that triggers ER stress mitochondrial apoptotic pathways in CNE cells. Taken together, these findings strongly suggest that polydatin might be a promising anti-tumor drug and our data provide the molecular theoretical basis for clinical application of polydatin.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, China. liaosmmu@126.com
authors.forename: Huanhai
authors.initials: H
authors.lastname: Liu
authors.forename: Shuwei
authors.initials: S
authors.lastname: Zhao
authors.forename: Yinfang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Hu
authors.initials: H
authors.lastname: Peng
authors.forename: Jingping
authors.initials: J
authors.lastname: Fan
authors.forename: Jianchun
authors.initials: J
authors.lastname: Liao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000473:pathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D013312:Stress, Physiological
chemical_list: D005960:Glucosides; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013267:Stilbenes; D045304:Cytochromes c; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; C058229:polydatin