Drug discovery and development of compounds from marine sponges

Our aim is to test if extracts and compounds derived from different sponges can inhibit tumor cell growth and trigger death in vitro and in vivo.

Marine derived compounds have been explored and considered as possible anti-tumor agents. Indeed, some natural products from marine organisms are currently in clinical trials e.g. Eribulin, an analogue of halichondrin B, isolated from the marine sponge Halichondria okadai, which is used for the treatment of metastatic breast cancer, and Trabectedin, isolated from Ecteinascidia turbinate, which has shown promising activity on metastatic soft-tissue sarcoma.

In an EU-funded project, SPECIAL (SPonge Enzymes and Cells for Innovative AppLications), we are searching for new compounds from sponges that can inhibit various tumor cell signaling mechanisms and induce tumor cell death. For that purpose sponges are collected at different locations and extracts are then tested for the capacity to cause tumor cell death, but without causing normal cell toxicity. Extracts showing tumor selective toxicity are further purified by HPLC fractionation until pure compound is generated. Large numbers of extracts from different sponges have been screened so far and we identified some compounds that hold promise as anti-tumor agents in different tumor types including lung cancer, ovarian carcinoma, breast cancer and different leukemias. We are trying to delineate how those compounds work within tumor cells and to describe signaling cascades that are altered upon exposure of tumor cells to such compounds. Finally, our findings will be verified in different tumor models in mice.

Publications

APS8, a polymeric alkylpyridinium salt blocks α7 nAChR and induces apoptosis in non-small cell lung carcinoma.
Zovko A, Viktorsson K, Lewensohn R, Kološa K, Filipič M, Xing H, et al
Mar Drugs 2013 Jul;11(7):2574-94

Chemical synthesis and biological activities of 3-alkyl pyridinium polymeric analogues of marine toxins.
Houssen W, Lu Z, Edrada-Ebel R, Chatzi C, Tucker S, Sepčić K, et al
J Chem Biol 2010 Feb;3(3):113-25

Zovko A, Vaukner Gabric M, Sepcic K, Pohleven F, Jaklic D, Gunde-Cimerman N, Lu Z, Edrada-Ebel R, Houssen WE, Mancini I, Defant A, Jaspars M, Turk T. Antifungal and antibacterial activity of 3-alkylpyridinium polymeric analogs of marine toxins. Int Biodeter Biodegr. 2012; 68:71-77.

Funding

Collaborations