title: Anti-migratory activity of marine alkaloid monanchocidin A - proteomics-based discovery and confirmation.
abstract: Monanchocidin A (MonA) is a novel marine alkaloid with promising anti-cancer properties. We recently demonstrated its high efficacy in human urogenital cancers including germ cell tumors. Here, we applied a global proteome screening approach to investigate molecular targets and biological processes affected by MonA in the human cisplatin-resistant germ cell cancer cell line NCCIT-R. Bioinformatical analysis of the proteomics data predicted an effect of MonA on cancer cell migration. Thus, proteins known to be involved in cancer cell migration and invasion were chosen for further validation. The protein alterations identified by proteomics resulted from both, regulation of the total protein expression and post-transcriptional modifications. Among others, regulation of an isoform of vimentin, up-regulation of multiple apolipoprotein E isoforms, and inhibition of hypusination of eukaryotic translation initiation factor 5A-1 were found upon treatment with MonA. Further functional analyses were performed and revealed decreased cell migration and colony formation of cancer cells treated with MonA at non-cytotoxic and non-antiproliferative concentrations. This work provides further insights into the molecular mechanisms behind MonA bioactivity. Furthermore, our research is exemplary for the ability of proteomics to predict drug targets and mode of action of natural anti-cancer agents.
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok, Russian Federation.|School of Natural Sciences, Far Eastern Federal University, Vladivostok, Russian Federation.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Dyshlovoy
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University of Greifswald, Greifswald, Germany.|Interfacultary Institute of Genetics and Functional Genomics, Department of Functional Genomics, University of Greifswald, Greifswald, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Venz
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hauschild
authors.affiliation: Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok, Russian Federation.
authors.forename: Ksenya M
authors.initials: KM
authors.lastname: Tabakmakher
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Otte
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ramin
authors.initials: R
authors.lastname: Madanchi
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University of Greifswald, Greifswald, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Walther
authors.affiliation: Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok, Russian Federation.
authors.forename: Alla G
authors.initials: AG
authors.lastname: Guzii
authors.affiliation: Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok, Russian Federation.
authors.forename: Tatyana N
authors.initials: TN
authors.lastname: Makarieva
authors.affiliation: Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok, Russian Federation.
authors.forename: Larisa K
authors.initials: LK
authors.lastname: Shubina
authors.affiliation: Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok, Russian Federation.
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Fedorov
authors.affiliation: Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Vladivostok, Russian Federation.
authors.forename: Valentin A
authors.initials: VA
authors.lastname: Stonik
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.affiliation: Division of Hematology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Balabanov
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Tumor and Breast Center ZeTuP St. Gallen, St. Gallen, Switzerland.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Honecker
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Gunhild
authors.initials: G
authors.lastname: V Amsberg
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression / Q000187:drug effects; D019791:Guanidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics
chemical_list: D000970:Antineoplastic Agents; D020543:Proteome; C554301:monanchocidin; D019791:Guanidine
keywords: Anti-migratory activity; Apolipoprotein E; Biomedicine; Germ cell tumor cells; Monanchocidin A; eIF5A