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ECB-ART-44841
Arch Toxicol 2017 Mar 01;913:1485-1495. doi: 10.1007/s00204-016-1787-7.
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Cytotoxic effects of the anthraquinone derivatives 1''-deoxyrhodoptilometrin and (S)-(-)-rhodoptilometrin isolated from the marine echinoderm Comanthus sp.

Wätjen W , Ebada SS , Bergermann A , Chovolou Y , Totzke F , Kubbutat MHG , Lin W , Proksch P .


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 (IC50 values: 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.

PubMed ID: 27473261
Article link: Arch Toxicol


Genes referenced: LOC100889782 LOC100889856 LOC100893907 LOC105441151 LOC115919910 ptk2