title: Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells.
abstract: Pancreatic cancer is one of the most aggressive cancer entities, with an extremely poor 5-year survival rate. Therefore, novel therapeutic agents with specific modes of action are urgently needed. Marine organisms represent a promising source to identify new pharmacologically active substances. Secondary metabolites derived from marine algae are of particular interest. The present work describes cellular and molecular mechanisms induced by an HPLC-fractionated, hydrophilic extract derived from the Baltic brown seaweed Fucus vesiculosus (Fv1). Treatment with Fv1 resulted in a strong inhibition of viability in various pancreatic cancer cell lines. This extract inhibited the cell cycle of proliferating cells due to the up-regulation of cell cycle inhibitors, shown on the mRNA (microarray data) and protein level. As a result, cells were dying in a caspase-independent manner. Experiments with non-dividing cells showed that proliferation is a prerequisite for the effectiveness of Fv1. Importantly, Fv1 showed low cytotoxic activity against non-malignant resting T cells and terminally differentiated cells like erythrocytes. Interestingly, accelerated killing effects were observed in combination with inhibitors of autophagy. Our in vitro data suggest that Fv1 may represent a promising new agent that deserves further development towards clinical application.
authors.affiliation: Division of Molecular Oncology, Institute for Experimental Cancer Research, Medical Faculty, CAU, University Hospital Schleswig-Holstein, 24105 Kiel, Germany. ugeisen@email.uni-kiel.de.
authors.forename: Ulf
authors.initials: U
authors.lastname: Geisen
authors.affiliation: CRM, Coastal Research & Management, 24159 Kiel, Germany. m.zenthoefer@web.de.
authors.forename: Marion
authors.initials: M
authors.lastname: Zenthoefer
authors.affiliation: Division of Stem Cell Transplantation and Immunotherapy, Department of Internal Medicine II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany. m.peipp@med2.uni-kiel.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Peipp
authors.affiliation: Division of Molecular Oncology, Institute for Experimental Cancer Research, Medical Faculty, CAU, University Hospital Schleswig-Holstein, 24105 Kiel, Germany. jannik-kerber@t-online.de.
authors.forename: Jannik
authors.initials: J
authors.lastname: Kerber
authors.affiliation: Institute of Immunology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany. Johannes.plenge@gmx.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Plenge
authors.affiliation: Department of Biology, University of Padua, 35131 Padua, Italy. manago.antonella@gmail.com.
authors.forename: Antonella
authors.initials: A
authors.lastname: Managò
authors.affiliation: Numares AG, 93053 Regensburg, Germany. markus.fuhrmann@numares.com.
authors.forename: Markus
authors.initials: M
authors.lastname: Fuhrmann
authors.affiliation: Numares AG, 93053 Regensburg, Germany. Roland.Geyer@numares.com.
authors.forename: Roland
authors.initials: R
authors.lastname: Geyer
authors.affiliation: CRM, Coastal Research & Management, 24159 Kiel, Germany. steffen.hennig@crm-online.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Hennig
authors.affiliation: Institute of Immunology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany. dadam@email.uni-kiel.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Adam
authors.affiliation: CRM, Coastal Research & Management, 24159 Kiel, Germany. lpiker@oceanbasis.de.
authors.forename: Levent
authors.initials: L
authors.lastname: Piker
authors.affiliation: Institute of Human Nutrition and Food Science, Christian-Albrechts University of Kiel, 24118 Kiel, Germany. rimbach@foodsci.uni-kiel.de.
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
authors.affiliation: Division of Molecular Oncology, Institute for Experimental Cancer Research, Medical Faculty, CAU, University Hospital Schleswig-Holstein, 24105 Kiel, Germany. hkalthoff@email.uni-kiel.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Kalthoff
mesh_terms: D001343:Autophagy / Q000187:drug effects; D020169:Caspases / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D044645:Fucus / Q000737:chemistry*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D010936:Plant Extracts; D020169:Caspases
keywords: Fucus vesiculosus; algae; autophagy; cancer; cell cycle inhibitors; pancreatic; proliferation