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

Geisen, Ulf, Zenthoefer, Marion, Peipp, Matthias, Kerber, Jannik, Plenge, Johannes, Manago, Antonella, Fuhrmann, Markus, Geyer, Roland, Hennig, Steffen, Adam, Dieter, Piker, Levent, Rimbach, Gerald and Kalthoff, Holger (2015) Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells Marine Drugs, 13 (7). pp. 4470-4491.

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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.

Document Type: Article
Additional Information: Times Cited: 0
Research affiliation: Kiel University
OceanRep > The Future Ocean - Cluster of Excellence
ISSN: 1660-3397
Projects: Future Ocean
Date Deposited: 20 Oct 2016 10:50
Last Modified: 20 Oct 2016 10:50
URI: http://eprints.uni-kiel.de/id/eprint/32486

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