CYANCAN: Uncovering the cyanobacterial chemical diversity: the search for novel anticancer compounds
Cancer has a tremendous negative socio-economic impact in our society. Treating cancer as a chronic disease is a well desired scenario for researchers and political stakeholders. Therefore, for improving quality of life is of utmost importance the discovery of new and more effective anticancer drugs. Hence, to address this societal challenge CYANCAN project has as main goal the discovery of novel anticancer compounds from cyanobacteria. These organisms have been regarded as one of the most promising groups of bacteria capable of producing metabolites with pharmaceutical applications. A valuable and underexplored natural resource that can underpin the discovery of promising compounds can be found within The Culture Collection of cyanobacteria (LEGEcc - CIIMAR), comprising more than 350 different cyanobacterial strains, collected in different ecosystems and locations. For this purpose, 150 LEGEcc strains belonging to Nostocales, Oscillatoriales, and Chroococcales orders will be screened for new and effective anticancer compounds. For the isolation of new chemical structures this project allies the classical bioassay-guided fractionation with the modern genome-based strategies. Genome mining approaches are powerful tools to find new compounds, through the exploitation of cyanobacterial biosynthetic gene clusters. As part of the strategy for finding robust anticancer lead compounds, this project will employ physiologically relevant cancer screening assays, as well as, addressing the main cancer multidrug resistance (MDR) mechanism. This will be accomplished by: i) using 3D cell culture of tumor spheroids; ii) evaluation of vascularization and metastasis in the zebrafish model iii) analyses of the involved molecular mechanisms; and iv) the study of the interaction between lead compounds and P-glycoprotein (ABCB1). Part of this work will be developed through the collaboration with international specialists form Karlsruhe Institute of Technology (KIT, Germany) and Szeged University (SZTE, Hungary). The promising lead compounds will possess a high added value that will be able to attract industrial partners for further drug development.