title: Costunolide, an active sesquiterpene lactone, induced apoptosis via ROS-mediated ER stress and JNK pathway in human U2OS cells.
abstract: Costunolide, an active sesquiterpene lactone, is derived from many herbal medicines and it exhibits a broad spectrum of bioactivities such as anti-inflammatory, potential anti-tumor activity. Herein we assessed the anti-cancer effects of costunolide on U2OS cells and explored the underlying molecular mechanisms. The experiment data show that Costunolide exhibited significant anti-tumor activity by apoptosis related assays including Annexin V-FITC/PI flow cytometric analysis and 4,6-diamino-2-phenyl indole (DAPI) staining morphological analysis. Furthermore, we found Costunolide induced the loss of mitochondrial transmembrane potential, down-regulated Bcl-2/Bax ratio, encouraged Cyt-c release and caspase activation. All those effects are contributed by reactive oxygen species (ROS) generation and ER stress-induced mitochondrial dysfunction which are also responsible for c-Jun N-terminal kinase (JNK) activation. After the treatment of JNK inhibitor SP600125, it obviously reversed costunolide-induced apoptosis. Given N-acetyl-l-cysteine (NAC) effectively blocked the activation of JNK. Taken together, our results demonstrate that costunolide induces apoptosis in human U2OS cells through ROS generation and p38 MAPK/JNK activation.
authors.affiliation: Department of Qrthopaedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China. Electronic address: zchao2015@163.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Qrthopaedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China.
authors.forename: Tan
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Qrthopaedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Wang
authors.affiliation: Department of Qrthopaedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Qrthopaedic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, China.
authors.forename: Ying-Feng
authors.initials: YF
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D007783:Lactones; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C002602:costunolide; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Costunolide; JNK; ROS; U2OS