title: Aaptamines from the marine sponge Aaptos sp. display anticancer activities in human cancer cell lines and modulate AP-1-, NF-κB-, and p53-dependent transcriptional activity in mouse JB6 Cl41 cells.
abstract: Aaptamine (8,9-dimethoxy-1H-benzo[de][1,6]naphthyridine) is a marine natural compound possessing antioxidative, antimicrobial, antifungal, and antiretroviral activity. Earlier, we have found that aaptamine and its derivatives demonstrate equal anticancer effects against the human germ cell cancer cell lines NT2 and NT2-R and cause some changes in the proteome of these cells. In order to explore further the mechanism of action of aaptamine and its derivatives, we studied the effects of aaptamine (1), demethyl(oxy)aaptamine (2), and isoaaptamine (3) on human cancer cell lines and on AP-1-, NF-κB-, and p53-dependent transcriptional activity in murine JB6 Cl41 cells. We showed that compounds 1-3 demonstrate anticancer activity in THP-1, HeLa, SNU-C4, SK-MEL-28, and MDA-MB-231 human cancer cell lines. Additionally, all compounds were found to prevent EGF-induced neoplastic transformation of murine JB6 Cl41 cells. Nuclear factors AP-1, NF-κB, and p53 are involved in the cellular response to high and nontoxic concentrations of aaptamine alkaloids 1-3. Furthermore, inhibition of EGF-induced JB6 cell transformation, which is exerted by the compounds 1-3 at low nontoxic concentrations of 0.7-2.1 μM, cannot be explained by activation of AP-1 and NF-κB.
authors.affiliation: Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch of the Russian Academy of Sciences, Prospect 100 Let Vladivostoku 159, Vladivostok 690022, Russia ; Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany ; School of Natural Sciences, Far East Federal University, Sukhanova Street 8, Vladivostok 690950, Russia.
authors.forename: Sergey A
authors.identifier: 0000-0002-7155-9245
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 of the Russian Academy of Sciences, Prospect 100 Let Vladivostoku 159, Vladivostok 690022, Russia.
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 of the Russian Academy of Sciences, Prospect 100 Let Vladivostoku 159, Vladivostok 690022, Russia.
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 of the Russian Academy of Sciences, Prospect 100 Let Vladivostoku 159, Vladivostok 690022, Russia.
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Kuzmich
authors.affiliation: Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.affiliation: Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
authors.forename: Gunhild
authors.initials: G
authors.lastname: Keller-von Amsberg
authors.affiliation: Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany ; Tumor and Breast Center ZeTuP St. Gallen, Rorschacherstraße 150, 9006 St. Gallen, Switzerland.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Honecker
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009287:Naphthyridines / Q000737:chemistry / Q000494:pharmacology*; D011161:Porifera / Q000737:chemistry*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D009287:Naphthyridines; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; C043986:aaptamine