title: Tricyclic guanidine alkaloids from the marine sponge Acanthella cavernosa that stabilize the tumor suppressor PDCD4.
abstract: A cell-based high-throughput screen that assessed the cellular stability of a tumor suppressor protein PDCD4 (Programmed cell death 4) was used to identify a new guanidine-containing marine alkaloid mirabilin K (3), as well as the known compounds mirabilin G (1) and netamine M (2). The structures of these tricyclic guanidine alkaloids were established from extensive spectroscopic analyses. Compounds 1 and 2 inhibited cellular degradation of PDCD4 with EC50 values of 1.8 μg/mL and 2.8 μg/mL, respectively. Mirabilin G (1) and netamine M (2) are the first marine natural products reported to stabilize PDCD4 under tumor promoting conditions.
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. t.grkovic@griffith.edu.au.
authors.forename: Tanja
authors.initials: T
authors.lastname: Grkovic
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. M_Bajer@gmx.de.
authors.forename: Johanna S
authors.initials: JS
authors.lastname: Blees
authors.affiliation: Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany. M_Bajer@gmx.de.
authors.forename: Magdalena M
authors.initials: MM
authors.lastname: Bayer
authors.affiliation: Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. colburna@mail.nih.gov.
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Colburn
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. cltterry@mail.nih.gov.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Thomas
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. henrichcj@mail.nih.gov.
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Henrich
authors.affiliation: Basic Science Program, Leidos Biomedical Research, Inc., Chemical Biology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. mpeach@helix.nih.gov.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Peach
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. mcmahoja@mail.nih.gov.
authors.forename: James B
authors.initials: JB
authors.lastname: McMahon
authors.affiliation: Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany. M_Bajer@gmx.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmid
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. gustafki@mail.nih.gov.
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Gustafson
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D019791:Guanidine / Q000737:chemistry* / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D011161:Porifera / Q000737:chemistry*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012503:Saponins / Q000737:chemistry; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D051017:Apoptosis Regulatory Proteins; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D012503:Saponins; D025521:Tumor Suppressor Proteins; C105644:mirabilin; D009828:Oleanolic Acid; D019791:Guanidine