title: Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro.
abstract: Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight rare guanidine alkaloids, recently isolated from the marine sponge Monanchora pulchra, namely: monanchocidin A (1), monanchocidin B (2), monanchomycalin C (3), ptilomycalin A (4), monanchomycalin B (5), normonanchocidin D (6), urupocidin A (7), and pulchranin A (8). All of the compounds induced cell cycle arrest (apart from 8) and programmed death of cancer cells. Ptilomycalin A-like compounds 1-6 activated JNK1/2 and ERK1/2, following AP-1 activation and caused p53-independent programmed cell death. Compound 7 induced p53-independent cell death without activation of AP-1 or caspase-3/7, and the observed JNK1/2 activation did not contribute to the cytotoxic effect of the compound. Alkaloid 8 induced JNK1/2 (but not ERK1/2) activation leading to p53-independent cell death and strong suppression of AP-1 activity. Alkaloids 1-4, 7, and 8 were able to inhibit the EGF-induced neoplastic transformation of JB6 P⁺ Cl41 cells. Our results suggest that investigated guanidine marine alkaloids hold potential to eliminate human cancer cells and prevent cancer cell formation and spreading.
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany. dyshlovoy@gmail.com.|Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Prospect 100-let Vladivostoku 159, Vladivostok 690022, Russia. dyshlovoy@gmail.com.|School of Natural Sciences, Far Eastern Federal University, Sukhanova Street 8, Vladivostok 690091, Russia. dyshlovoy@gmail.com.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Dyshlovoy
authors.affiliation: Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Prospect 100-let Vladivostoku 159, Vladivostok 690022, Russia. xen-tab@yandex.ru.
authors.forename: Kseniya M
authors.initials: KM
authors.lastname: Tabakmakher
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany. j.hauschild@uke.de.
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, Prospect 100-let Vladivostoku 159, Vladivostok 690022, Russia. flagmandv@inbox.ru.
authors.forename: Regina K
authors.initials: RK
authors.lastname: Shchekaleva
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany. k.otte@uke.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Otte
authors.affiliation: Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Prospect 100-let Vladivostoku 159, Vladivostok 690022, Russia. gagry@rambler.ru.
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, Prospect 100-let Vladivostoku 159, Vladivostok 690022, Russia. makarieva@piboc.dvo.ru.
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, Prospect 100-let Vladivostoku 159, Vladivostok 690022, Russia. catrinog.81@mail.ru.
authors.forename: Ekaterina K
authors.initials: EK
authors.lastname: Kudryashova
authors.affiliation: Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Prospect 100-let Vladivostoku 159, Vladivostok 690022, Russia. fedorov@piboc.dvo.ru.
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, Prospect 100-let Vladivostoku 159, Vladivostok 690022, Russia. shubina@piboc.dvo.ru.
authors.forename: Larisa K
authors.initials: LK
authors.lastname: Shubina
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany. c.bokemeyer@uke.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany. friedemann.honecker@zetup.ch.|Tumor and Breast Center ZeTuP St. Gallen, Rorschacher Strasse 150, St. Gallen 9006, Switzerland. friedemann.honecker@zetup.ch.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Honecker
authors.affiliation: Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Prospect 100-let Vladivostoku 159, Vladivostok 690022, Russia. stonik@piboc.dvo.ru.
authors.forename: Valentin A
authors.initials: VA
authors.lastname: Stonik
authors.affiliation: Laboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany. g.von-amsberg@uke.de.
authors.forename: Gunhild
authors.initials: G
authors.lastname: von Amsberg
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D019791:Guanidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D006146:Guanidines / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D011161:Porifera / Q000737:chemistry*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000470:Alkaloids; D006146:Guanidines; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; C554301:monanchocidin; C585942:monanchomycalin C; C103200:ptilomycalin A; C000597826:urupocidin A; D004815:Epidermal Growth Factor; D019791:Guanidine
keywords: AP-1; MAPK; Monanchora pulchra; apoptosis; guanidine alkaloids; monanchocidin A; neoplastic transformation