title: Costunolide Induces Apoptosis through Generation of ROS and Activation of P53 in Human Esophageal Cancer Eca-109 Cells.
abstract: Costunolide is a sesquiterpene lactone, which possesses potent anti-cancer properties. However, there is little report about its effects on esophageal cancer. In our study, we investigated the effects of costunolide on the cell viability, cell cycle, and apoptosis in human esophageal cancer Eca-109 cells. It was found that costunolide inhibited the growth of Eca-109 cells in a dose-dependent manner, which was associated with the loss of mitochondrial membrane potential (Δψm ) and the production of ROS. Costunolide induced apoptosis of Eca-109 cells as well as cell cycle arrest in G1/S phase by upregulation of P53 and P21. Costunolide triggered apoptosis in esophageal cancer cells via the upregulation of Bax, downregulation of Bcl-2, and significant activation of caspase-3 and poly ADP-ribose polymerase. These effects were markedly abrogated when cells were pretreated with N-acetylcysteine, a specific reactive oxygen specie inhibitor. These results suggest that costunolide is a potential candidate for the treatment of esophageal cancer.
authors.affiliation: Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, 130041, People's Republic of China.
authors.forename: Peiyan
authors.initials: P
authors.lastname: Hua
authors.affiliation: Department of Pathology, The Second Hospital of Jilin University, Changchun, 130041, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, 130041, People's Republic of China.
authors.forename: Guangxin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, 130041, People's Republic of China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, 130041, People's Republic of China.
authors.forename: Ge
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Breast surgery, The First Hospital of Jilin University, Changchun, 130021, People's Republic of China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, 130041, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, 130041, People's Republic of China.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, 130041, People's Republic of China. bingjinli@hotmail.com.
authors.forename: Bingjin
authors.initials: B
authors.lastname: Li
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D005786:Gene Expression Regulation; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D007783:Lactones
chemical_list: D000111:Acetylcysteine; D000972:Antineoplastic Agents, Phytogenic; D053148:Caspase 3; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016166:Free Radical Scavengers; D011065:Poly(ADP-ribose) Polymerases; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C000595707:BCL2 protein, human; C002602:costunolide; D007783:Lactones; C505407:CASP3 protein, human
keywords: Apoptosis; Costunolide; G1/S Phase; ROS; Sophageal Cancer