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Mycalamide A Shows Cytotoxic Properties and Prevents EGF-Induced Neoplastic Transformation through Inhibition of Nuclear Factors
Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Paciﬁc Institute of Bioorganic Chemistry, Far-East Branch of the Russian Academy of Sciences, Prospect 100-let Vladivostoku 159, Vladivostok 690022, Russia
Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Martinistr. 52, Hamburg 20246, Germany
School of Natural Sciences, Far Eastern Federal University, Sukhanova Street, 8, Vladivostok 690091, Russia
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 31 March 2012; in revised form: 15 May 2012 / Accepted: 21 May 2012 / Published: 30 May 2012
Abstract: Mycalamide A, a marine natural compound previously isolated from sponges, is known as a protein synthesis inhibitor with potent antitumor activity. However, the ability of this compound to prevent malignant transformation of cells has never been examined before. Here, for the first time, we report the isolation of mycalamide A from ascidian Polysincraton sp. as well as investigation of its cancer preventive properties. In murine JB6 Cl41 P+ cells, mycalamide A inhibited epidermal growth factor (EGF)-induced neoplastic transformation, and induced apoptosis at subnanomolar or nanomolar concentrations. The compound inhibited transcriptional activity of the oncogenic nuclear factors AP-1 and NF-κB, a potential mechanism of its cancer preventive properties. Induction of phosphorylation of the kinases MAPK p38, JNK, and ERK was also observed at high concentrations of mycalamide A. The drug shows promising potential for both cancer-prevention and cytotoxic therapy and should be further developed.
Keywords: mycalamide A; Polysincraton sp.; cancer preventive activity; apoptosis; AP-1; NF-κB; p53
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Dyshlovoy, S.A.; Fedorov, S.N.; Kalinovsky, A.I.; Shubina, L.K.; Bokemeyer, C.; Stonik, V.A.; Honecker, F. Mycalamide A Shows Cytotoxic Properties and Prevents EGF-Induced Neoplastic Transformation through Inhibition of Nuclear Factors. Mar. Drugs 2012, 10, 1212-1224.
Dyshlovoy SA, Fedorov SN, Kalinovsky AI, Shubina LK, Bokemeyer C, Stonik VA, Honecker F. Mycalamide A Shows Cytotoxic Properties and Prevents EGF-Induced Neoplastic Transformation through Inhibition of Nuclear Factors. Marine Drugs. 2012; 10(6):1212-1224.
Dyshlovoy, Sergey A.; Fedorov, Sergey N.; Kalinovsky, Anatoly I.; Shubina, Larisa K.; Bokemeyer, Carsten; Stonik, Valentin A.; Honecker, Friedemann. 2012. "Mycalamide A Shows Cytotoxic Properties and Prevents EGF-Induced Neoplastic Transformation through Inhibition of Nuclear Factors." Mar. Drugs 10, no. 6: 1212-1224.