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Open AccessArticle

Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells

1
Division of Molecular Oncology, Institute for Experimental Cancer Research, Medical Faculty, CAU, University Hospital Schleswig-Holstein, 24105 Kiel, Germany
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CRM, Coastal Research & Management, 24159 Kiel, Germany
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Division of Stem Cell Transplantation and Immunotherapy, Department of Internal Medicine II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany
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Institute of Immunology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany
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Department of Biology, University of Padua, 35131 Padua, Italy
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Numares AG, 93053 Regensburg, Germany
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Institute of Human Nutrition and Food Science, Christian-Albrechts University of Kiel, 24118 Kiel, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Peer B. Jacobson
Mar. Drugs 2015, 13(7), 4470-4491; https://doi.org/10.3390/md13074470
Received: 4 June 2015 / Revised: 7 July 2015 / Accepted: 8 July 2015 / Published: 20 July 2015
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. View Full-Text
Keywords: algae; Fucus vesiculosus; pancreatic; cancer; cell cycle inhibitors; autophagy; proliferation algae; Fucus vesiculosus; pancreatic; cancer; cell cycle inhibitors; autophagy; proliferation
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MDPI and ACS Style

Geisen, U.; Zenthoefer, M.; Peipp, M.; Kerber, J.; Plenge, J.; Managò, A.; Fuhrmann, M.; Geyer, R.; Hennig, S.; Adam, D.; Piker, L.; Rimbach, G.; Kalthoff, H. Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells. Mar. Drugs 2015, 13, 4470-4491. https://doi.org/10.3390/md13074470

AMA Style

Geisen U, Zenthoefer M, Peipp M, Kerber J, Plenge J, Managò A, Fuhrmann M, Geyer R, Hennig S, Adam D, Piker L, Rimbach G, Kalthoff H. Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells. Marine Drugs. 2015; 13(7):4470-4491. https://doi.org/10.3390/md13074470

Chicago/Turabian Style

Geisen, Ulf; Zenthoefer, Marion; Peipp, Matthias; Kerber, Jannik; Plenge, Johannes; Managò, Antonella; Fuhrmann, Markus; Geyer, Roland; Hennig, Steffen; Adam, Dieter; Piker, Levent; Rimbach, Gerald; Kalthoff, Holger. 2015. "Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells" Mar. Drugs 13, no. 7: 4470-4491. https://doi.org/10.3390/md13074470

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