title: Mycalamide A shows cytotoxic properties and prevents EGF-induced neoplastic transformation through inhibition of nuclear factors.
abstract: Mycalamide A, a marine natural compound previously isolated from sponges, is known as a protein synthesis inhibitor with potent antitumor activity. However, the ability of this compound to prevent malignant transformation of cells has never been examined before. Here, for the first time, we report the isolation of mycalamide A from ascidian Polysincraton sp. as well as investigation of its cancer preventive properties. In murine JB6 Cl41 P(+) cells, mycalamide A inhibited epidermal growth factor (EGF)-induced neoplastic transformation, and induced apoptosis at subnanomolar or nanomolar concentrations. The compound inhibited transcriptional activity of the oncogenic nuclear factors AP-1 and NF-κB, a potential mechanism of its cancer preventive properties. Induction of phosphorylation of the kinases MAPK p38, JNK, and ERK was also observed at high concentrations of mycalamide A. The drug shows promising potential for both cancer-prevention and cytotoxic therapy and should be further developed.
authors: 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, Martinistr. 52, Hamburg 20246, Germany.
authors: Sergey A
authors: 0000-0002-7155-9245
authors: SA
authors: Dyshlovoy
authors: 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: Sergey N
authors: SN
authors: Fedorov
authors: 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: Anatoly I
authors: AI
authors: Kalinovsky
authors: 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: Larisa K
authors: LK
authors: Shubina
authors: Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg 20246, Germany.
authors: Carsten
authors: C
authors: Bokemeyer
authors: 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.|School of Natural Sciences, Far Eastern Federal University, Sukhanova Street, 8, Vladivostok 690091, Russia.
authors: Valentin A
authors: VA
authors: Stonik
authors: Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg 20246, Germany.
authors: Friedemann
authors: F
authors: Honecker
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011714:Pyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D014158:Transcription, Genetic / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors; D014561:Urochordata; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D011714:Pyrans; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; C059646:mycalamide A; D004815:Epidermal Growth Factor; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4