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Mar. Drugs 2016, 14(7), 133; doi:10.3390/md14070133

Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro

1
Laboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany
2
Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, Prospect 100-let Vladivostoku 159, Vladivostok 690022, Russia
3
School of Natural Sciences, Far Eastern Federal University, Sukhanova Street 8, Vladivostok 690091, Russia
4
Tumor and Breast Center ZeTuP St. Gallen, Rorschacher Strasse 150, St. Gallen 9006, Switzerland
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Kirsten Benkendorff
Received: 18 May 2016 / Revised: 5 July 2016 / Accepted: 8 July 2016 / Published: 15 July 2016
(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)
View Full-Text   |   Download PDF [4244 KB, uploaded 15 July 2016]   |  

Abstract

Guanidine alkaloids from sponges Monanchora spp. represent diverse bioactive compounds, however, the mechanisms underlying bioactivity are very poorly understood. Here, we report results of studies on cytotoxic action, the ability to inhibit EGF-induced neoplastic transformation, and the effects on MAPK/AP-1 signaling of eight rare guanidine alkaloids, recently isolated from the marine sponge Monanchora pulchra, namely: monanchocidin A (1), monanchocidin B (2), monanchomycalin C (3), ptilomycalin A (4), monanchomycalin B (5), normonanchocidin D (6), urupocidin A (7), and pulchranin A (8). All of the compounds induced cell cycle arrest (apart from 8) and programmed death of cancer cells. Ptilomycalin A-like compounds 16 activated JNK1/2 and ERK1/2, following AP-1 activation and caused p53-independent programmed cell death. Compound 7 induced p53-independent cell death without activation of AP-1 or caspase-3/7, and the observed JNK1/2 activation did not contribute to the cytotoxic effect of the compound. Alkaloid 8 induced JNK1/2 (but not ERK1/2) activation leading to p53-independent cell death and strong suppression of AP-1 activity. Alkaloids 14, 7, and 8 were able to inhibit the EGF-induced neoplastic transformation of JB6 P+ Cl41 cells. Our results suggest that investigated guanidine marine alkaloids hold potential to eliminate human cancer cells and prevent cancer cell formation and spreading. View Full-Text
Keywords: guanidine alkaloids; monanchocidin A; Monanchora pulchra; apoptosis; MAPK; AP-1; neoplastic transformation guanidine alkaloids; monanchocidin A; Monanchora pulchra; apoptosis; MAPK; AP-1; neoplastic transformation
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MDPI and ACS Style

Dyshlovoy, S.A.; Tabakmakher, K.M.; Hauschild, J.; Shchekaleva, R.K.; Otte, K.; Guzii, A.G.; Makarieva, T.N.; Kudryashova, E.K.; Fedorov, S.N.; Shubina, L.K.; Bokemeyer, C.; Honecker, F.; Stonik, V.A.; von Amsberg, G. Guanidine Alkaloids from the Marine Sponge Monanchora pulchra Show Cytotoxic Properties and Prevent EGF-Induced Neoplastic Transformation in Vitro. Mar. Drugs 2016, 14, 133.

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