title: Chlorogenic acid induces apoptotic cell death in U937 leukemia cells through caspase- and mitochondria-dependent pathways.
abstract: Chlorogenic acid exists widely in edible and medicinal plants and acts as an antioxidant. It is known to exert antitumor activity via induction of apoptosis in many human cancer cells. However, its signaling pathway in human leukemia cells still remains unclear. Therefore, we investigated the roles of reactive oxygen species (ROS), mitochondria and caspases during chlorogenic acid-induced apoptosis of U937 human leukemia cells. Chlorogenic acid exhibited a strong cytotoxicity and induced apoptosis in U937 cells, as determined by 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Chlorogenic acid induced apoptosis by promoting ROS production and reduced the mitochondrial membrane potential (ΔΨm), as assayed by flow cytometry. Furthermore, the activity of caspase-3 was evaluated and results indicated that chlorogenic acid promoted caspase-3 activity in U937 cells. Results from western blot analysis showed that chlorogenic acid promoted expression of caspase-3, -7, -8 and -9 in U937 cells. Taken together, these results suggest that chlorogenic acid may induce apoptosis by reducing the levels of ΔΨm and by increasing the activation of caspase-3 pathways in human leukemia U937 cells in vitro.
authors.affiliation: Department of Pharmacology, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Che-Wei
authors.initials: CW
authors.lastname: Liu
authors.forename: Yi-Shih
authors.initials: YS
authors.lastname: Ma
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Weng
authors.forename: Nou-Ying
authors.initials: NY
authors.lastname: Tang
authors.forename: Shin-Hwar
authors.initials: SH
authors.lastname: Wu
authors.forename: Bin-Chuani
authors.initials: BC
authors.lastname: Ji
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Ma
authors.forename: Yang-Ching
authors.initials: YC
authors.lastname: Ko
authors.forename: Shinji
authors.initials: S
authors.lastname: Funayama
authors.forename: Chao-Lin
authors.initials: CL
authors.lastname: Kuo
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002726:Chlorogenic Acid / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D020298:U937 Cells
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D002726:Chlorogenic Acid; D053148:Caspase 3