title: Smenospongidine suppresses the proliferation of multiple myeloma cells by promoting CCAAT/enhancer-binding protein homologous protein-mediated β-catenin degradation.
abstract: Abnormal up-regulation of β-catenin expression is associated with the development and progression of multiple myeloma and is thus a potential therapeutic target. Here, we screened cell-based natural compounds and identified smenospongidine, a metabolite isolated from a marine sponge, as an antagonist of the Wnt/β-catenin signaling pathway. Smenospongidine promoted the degradation of intracellular β-catenin that accumulated via Wnt3a or 6-bromoindirubin-3'-oxime, an inhibitor of glycogen synthase kinase-3β. Consistently, smenospongidine down-regulated β-catenin expression and repressed the levels of β-catenin/T cell factor-dependent genes such as axin2, c-myc, and cyclin D1 in RPMI-8226 multiple myeloma cells. Smenospongidine suppressed proliferation and significantly induced apoptosis in RPMI-8266 cells. In addition, smenospongidine-induced β-catenin degradation was mediated by up-regulating CCAAT/enhancer-binding protein homologous protein (CHOP). These findings indicate that smenospongidine exerts its anti-proliferative activity by blocking the Wnt/β-catenin signaling pathway and may be a potential chemotherapeutic agent against multiple myeloma.
authors.affiliation: Department of Bio and Fermentation Convergence Technology, BK21 PLUS program, Kookmin University, Seoul, 02707, Republic of Korea.
authors.forename: Seoyoung
authors.initials: S
authors.lastname: Park
authors.affiliation: College of Pharmacy, Woosuk University, Wanju, Jeonbuk, 55338, Republic of Korea.
authors.forename: In Hyun
authors.initials: IH
authors.lastname: Hwang
authors.affiliation: Department of Bio and Fermentation Convergence Technology, BK21 PLUS program, Kookmin University, Seoul, 02707, Republic of Korea.
authors.forename: Jiseon
authors.initials: J
authors.lastname: Kim
authors.affiliation: BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: Gyu-Young
authors.initials: GY
authors.lastname: Song
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea. mkna@cnu.ac.kr.
authors.forename: MinKyun
authors.initials: M
authors.lastname: Na
authors.affiliation: Department of Bio and Fermentation Convergence Technology, BK21 PLUS program, Kookmin University, Seoul, 02707, Republic of Korea. ohsa@kookmin.ac.kr.|Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul, 02707, Republic of Korea. ohsa@kookmin.ac.kr.
authors.forename: Sangtaek
authors.initials: S
authors.lastname: Oh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D011161:Porifera / Q000737:chemistry; D011809:Quinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D022782:CCAAT-Enhancer-Binding Protein-beta; D011809:Quinones; D012717:Sesquiterpenes; D051176:beta Catenin; C489442:smenospongine
keywords: CCAAT/enhancer-binding protein homologous protein (CHOP); Multiple myeloma; Smenospongidine; β-catenin degradation