Projects / Programmes
Anticarcinogenic activity of bioactive compounds from cyanobacterial source in the progression of brain tumours - glioblastoma.
| Code |
Science |
Field |
Subfield |
| 1.03.00 |
Natural sciences and mathematics |
Biology |
|
| Code |
Science |
Field |
| P004 |
Natural sciences and mathematics |
Biochemistry, Metabolism |
| P310 |
Natural sciences and mathematics |
Proteins, enzymology |
| B000 |
Biomedical sciences |
|
| B200 |
Biomedical sciences |
Cytology, oncology, cancerology |
Cyanobacteria, cyclic peptides, elastaase, enzyme kinetics, glioblastoma, invasion, stem cells, mesenchymal stem cells (MSC), prognostic biomarkers, cancer therapeutics
Researchers (12)
Organisations (2)
Abstract
Biological characteristics of natural agents from various organisms have been used for thousands of years in treatment of various diseases, including cancer. Here, we want to investigate the activity of non-toxic cyclic peptides, produced by cyanobacteria (CP), on various human cells that constitute the heterogeneous population of malignant glioblastoma (GBM) microenvironment and consider the possibilities of their application in various principles of treatments. GBM are the most common, most malignant and unfortunately most incurable among all brain tumours. Therapeutic targets may not only be the GBM cells themselves, but also various tumour supporting stromal cells, such as neutrophyl leucocytes.
»Non-toxic« cyclic peptides possess several biological activities that could be used in anticancer treatment. These are the inhibition of proteolytic activity, possible interactions with mammalian cell cytoskeleton and the newly discovered ability of lysis induction in virally infected prokaryotic cells. We will test these activities in two types of CPs, cyclic depsipeptide planktopeptin BL 1125 (PP BL) and cyclic peptide with ureido linkage anabenopeptines B (AnP B) and F (AnP F), isolated from cyanobacterial species Planktothrix rubescens. Specifically:
- We will study the kinetic parameters of the mentioned CPs to define their target proteases and their potential further application in GBM.
- Partially characterised effects of CPs on cytoskeleton protein polymerisation and their impact on cell migration will be tested in migratory GBM cells and neutrophyl leucocytes.
- We will test the CPs ability to induce the lytic cycle in virally transfected human cells. The confirmation of such mechanisms will also be carried out on human mesenchymal stem cells (hMSC), which are potential new therapeutic cell vectors for GBM.
Significance for science
Unique interdisciplinarity, which links the research of cyanobacterial secondary metabolites with gene analysis (toxicogenomics) and with study of the metabolite effect on normal and tumour cells (carcinogenesis), offer many advantages and originality of scientific results. New results on different CCP add to our understanding of many biological processes and contribute to understanding the threat cyanobacterial metabolites present to water environment.
We obtained very useful ecotoxicological data, which are crucial for environmental risk assessment and for establishment of the appropriate preventive steps concerning environmental, animal and human exposures. We determined the role and impact of CCP in natural environment and contributed considerably to the faster development of new ecotoxicological methods and targets that is important for human health. Our results present very important information about the role and significance of selected cyanobacterial peptides. Further, we were the first to thoroughlyl characterize their inhibitory activities.
Our group collaborates with many scientific institutes from Slovenia and abroad on several different fields and these connections are effective in the knowledge transfer and enable us to work using new technologies.
Significance for the country
Cyanobacterial blooms in relation to the eutrophication of surface waters are common events worldwide and in Slovenia. Therefore cyanobacteria and their metabolites present a good model for estimating the threat of cyanobacterial population to water bodies and also to humans. These results on in vitro cell models provide some interesting data for new pharmaceutical drugs design and also for preventing the negative effects on human health.
The results in the field of ecotoxicological provide an important data for improvement of Slovenian water legislation and promote ecotoxicological monitoring of surface water status in Slovenia and affect the national economy as the changes of nature safety policy could positively influence the climate changes.
Newly developed methodology of IC staining of cyanobacteria and other phytoplankton organisms opens way to many applications that could be offered on the market; following up the cyanobacterial fitness, identification of cyanobacterial and phytoplankton strains and the most important - following up the cyanobacterial bloom lysis.
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
