title: Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells.
abstract: We investigated the molecular mechanisms responsible for fisetin-induced apoptosis in U266 cells. Fisetin elicited the cytotoxicity in U266 cells, manifested as an increased fraction of the cells with sub-G1 content or stained positively with TUNEL labeling. Fisetin enhanced caspase-3 activation, downregulation of Bcl-2 and Mcl-1(L), and upregulation of Bax, Bim and Bad. Fisetin activated AMPK as well as its substrate acetyl-CoA carboxylase (ACC), along with a decreased phosphorylation of AKT and mTOR. Fisetin also stimulated generation of ROS in U266 cells. Conversely, compound C or N-acetyl-L-cystein blocked fisetin-induced apoptosis. Our data suggest that fisetin-induced apoptosis in U266 cells is through ROS and AMPK pathways.
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Jang
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Jeong
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jung
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Wonil
authors.initials: W
authors.lastname: Koh
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Chang-Yan
authors.initials: CY
authors.lastname: Chen
authors.affiliation: College of Oriental Medicine, Kyung Hee University, Seoul 130-701, South Korea. Electronic address: sungkim7@khu.ac.kr.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D044948:Flavonols; D017382:Reactive Oxygen Species; D055372:AMP-Activated Protein Kinases; C017875:fisetin