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

• Published in: Marine drugs Vol. 14; no. 7; p. 133
• Main Authors: Dyshlovoy, Sergey A, Tabakmakher, Kseniya M, Hauschild, Jessica, Shchekaleva, Regina K, Otte, Katharina, Guzii, Alla G, Makarieva, Tatyana N, Kudryashova, Ekaterina K, Fedorov, Sergey N, Shubina, Larisa K, Bokemeyer, Carsten, Honecker, Friedemann, Stonik, Valentin A, von Amsberg, Gunhild
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 15.07.2016; MDPI AG
• Subjects: Alkaloids - chemistry; Alkaloids - pharmacology; Animals; AP-1; apoptosis; Cell Cycle Checkpoints - drug effects; Cell Death - drug effects; Cell Line; Cell Line, Tumor; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - metabolism; Epidermal Growth Factor - metabolism; Guanidine - analogs & derivatives; Guanidine - chemistry; Guanidine - pharmacology; guanidine alkaloids; Guanidines - chemistry; Guanidines - pharmacology; HeLa Cells; Humans; MAP Kinase Signaling System - drug effects; MAPK; Mice; monanchocidin A; Monanchora pulchra; neoplastic transformation; Porifera - chemistry; Transcription Factor AP-1 - metabolism; Tumor Suppressor Protein p53 - metabolism; Monanchora pulchra; monanchocidin A; neoplastic transformation; apoptosis; guanidine alkaloids; MAPK; AP-1
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md14070133

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 1-6 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 1-4, 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.