title: Cytotoxic effects of the anthraquinone derivatives 1'-deoxyrhodoptilometrin and (S)-(-)-rhodoptilometrin isolated from the marine echinoderm Comanthus sp.
abstract: We investigated cytotoxic effects of the anthraquinone derivatives 1'-deoxyrhodoptilometrin (SE11) and (S)-(-)-rhodoptilometrin (SE16) isolated from the marine echinoderm Comanthus sp. in two tumor cell lines (C6 glioma, Hct116 colon carcinoma). Both compounds showed cytotoxic effects, with SE11 [IC50-value (MTT assay): 13.1 µM in Hct116 cells] showing a higher potency to induce apoptotic and necrotic cell death. No generation of oxidative stress was detectable (DCF assay), and also no modulation of Nrf2/ARE and NFκB signaling could be shown. Investigation of 23 protein kinases associated with cell proliferation, survival, metastasis, and angiogenesis showed that both compounds were potent inhibitors of distinct kinases, e.g., IGF1-receptor kinase, focal adhesion kinase, and EGF receptor kinase with SE11 being a more potent compound (IC50values: 5, 18.4 and 4 µM, respectively). SE11 caused a decrease in ERK phosphorylation which may be a consequence of the inhibition of EGF receptor kinase by this compound. Since an inhibition of the EGF receptor/MAPK pathway is an important target for diverse cytostatic drugs, we suggest that the anthraquinone derivative 1'-deoxyrhodoptilometrin (SE11) may be an interesting lead structure for the development of new anticancer drugs.
authors.affiliation: Biofunctionality of Secondary Plant Compounds, Institute of Agricultural and Nutritional Sciences, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120, Halle/Saale, Germany. wim.waetjen@landw.uni-halle.de.|Institute of Toxicology, Heinrich-Heine-Universität, P.O. Box 101007, 40001, Düsseldorf, Germany. wim.waetjen@landw.uni-halle.de.
authors.forename: Wim
authors.initials: W
authors.lastname: Wätjen
authors.affiliation: Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität, Universitätsstr. 1, 40225, Düsseldorf, Germany.|Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street 1, Cairo, 11566, Egypt.
authors.forename: Sherif S
authors.initials: SS
authors.lastname: Ebada
authors.affiliation: Institute of Toxicology, Heinrich-Heine-Universität, P.O. Box 101007, 40001, Düsseldorf, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Bergermann
authors.affiliation: Institute of Toxicology, Heinrich-Heine-Universität, P.O. Box 101007, 40001, Düsseldorf, Germany.
authors.forename: Yvonni
authors.initials: Y
authors.lastname: Chovolou
authors.affiliation: ProQinase GmbH, Breisacher Str. 117, 79106, Freiburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Totzke
authors.affiliation: ProQinase GmbH, Breisacher Str. 117, 79106, Freiburg, Germany.
authors.forename: Michael H G
authors.initials: MHG
authors.lastname: Kubbutat
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Lin
authors.affiliation: Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-Universität, Universitätsstr. 1, 40225, Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Proksch
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D061745:Antioxidant Response Elements / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004447:Echinodermata / Q000737:chemistry*; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D045325:HCT116 Cells / Q000187:drug effects; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism
chemical_list: C000614672:1'-deoxyrhodoptilometrin; D000880:Anthraquinones; D000970:Antineoplastic Agents; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; C000614671:rhodoptilometrin; D011494:Protein Kinases
keywords: ARE; Apoptosis; Cytotoxicity; EGFR; ERK; NF-κB; Nrf2; Protein kinase