{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T11:13:15Z","timestamp":1767611595977,"version":"build-2065373602"},"reference-count":67,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["20-04-00923","20-04-00089"],"award-info":[{"award-number":["20-04-00923","20-04-00089"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-14-00355"],"award-info":[{"award-number":["21-14-00355"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2019-1660"],"award-info":[{"award-number":["075-15-2019-1660"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Myeloid leukemia is a hematologic neoplasia characterized by a clonal proliferation of hematopoietic stem cell progenitors. Patient prognosis varies depending on the subtype of leukemia as well as eligibility for intensive treatment regimens and allogeneic stem cell transplantation. Although significant progress has been made in the therapy of patients including novel targeted treatment approaches, there is still an urgent need to optimize treatment outcome. The most common therapy is based on the use of chemotherapeutics cytarabine and anthrayclines. Here, we studied the effect of the recently synthesized marine alkaloid 3,10-dibromofascaplysin (DBF) in myeloid leukemia cells. Unsubstituted fascaplysin was early found to affect cell cycle via inhibiting CDK4\/6, thus we compared the activity of DBF and other brominated derivatives with known CDK4\/6 inhibitor palbociclib, which was earlier shown to be a promising candidate to treat leukemia. Unexpectedly, the effect DBF on cell cycle differs from palbociclib. In fact, DBF induced leukemic cells apoptosis and decreased the expression of genes responsible for cancer cell survival. Simultaneously, DBF was found to activate the E2F1 transcription factor. Using bioinformatical approaches we evaluated the possible molecular mechanisms, which may be associated with DBF-induced activation of E2F1. Finally, we found that DBF synergistically increase the cytotoxic effect of cytarabine in different myeloid leukemia cell lines. In conclusion, DBF is a promising drug candidate, which may be used in combinational therapeutics approaches to reduce leukemia cell growth.<\/jats:p>","DOI":"10.3390\/md19090489","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T22:49:51Z","timestamp":1630363791000},"page":"489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Cytotoxic Marine Alkaloid 3,10-Dibromofascaplysin Induces Apoptosis and Synergizes with Cytarabine Resulting in Leukemia Cell Death"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0610-5079","authenticated-orcid":false,"given":"Pavel","family":"Spirin","sequence":"first","affiliation":[{"name":"Department of Cancer Cell Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, 119991 Moscow, Russia"},{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0361-6359","authenticated-orcid":false,"given":"Elena","family":"Shyrokova","sequence":"additional","affiliation":[{"name":"Department of Cancer Cell Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, 119991 Moscow, Russia"},{"name":"Moscow Institute of Physics and Technology (National Research University), Institutskiy Per. 9, 141701 Dolgoprudny, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5966-0914","authenticated-orcid":false,"given":"Timofey","family":"Lebedev","sequence":"additional","affiliation":[{"name":"Department of Cancer Cell Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, 119991 Moscow, Russia"},{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elmira","family":"Vagapova","sequence":"additional","affiliation":[{"name":"Department of Cancer Cell Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, 119991 Moscow, Russia"},{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Polina","family":"Smirnova","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Far Eastern Federal University, FEFU Campus, Ajax Bay 10, Russky Island, 690922 Vladivostok, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey","family":"Kantemirov","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Far Eastern Federal University, FEFU Campus, Ajax Bay 10, Russky Island, 690922 Vladivostok, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7155-9245","authenticated-orcid":false,"given":"Sergey A.","family":"Dyshlovoy","sequence":"additional","affiliation":[{"name":"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, 20251 Hamburg, Germany"},{"name":"Martini-Klinik, Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20251 Hamburg, Germany"},{"name":"Laboratory of Pharmacology, A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, Palchevskogo Str. 17, 690041 Vladivostok, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunhild von","family":"Amsberg","sequence":"additional","affiliation":[{"name":"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, 20251 Hamburg, Germany"},{"name":"Martini-Klinik, Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxim","family":"Zhidkov","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Far Eastern Federal University, FEFU Campus, Ajax Bay 10, Russky Island, 690922 Vladivostok, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Prassolov","sequence":"additional","affiliation":[{"name":"Department of Cancer Cell Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, 119991 Moscow, Russia"},{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2217\/ijh-2017-0002","article-title":"Understanding the molecular basis of acute myeloid leukemias: Where are we now?","volume":"6","author":"Gruszka","year":"2017","journal-title":"Int. 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