Human defense peptides as novel agents against cancer
Description: Each year 10.9 million people worldwide are diagnosed with cancer and there are 6.7 million deaths from this disease. It is estimated that there are 24.6 million people alive who have received a diagnosis of cancer in the last five years. Although much progress has been achieved concerning therapies in the last decades, surgery, chemotherapies or radiation are not successful in more than 50% of the cases and for those who survive, strong adverse reactions and the risk of reoccurrence of the disease represents a big problem. In this project we copy and enforce a weapon of the immune system against degenerated cells in the form of small cationic peptides that are important components of the innate immune system of all species. Some of these amphipathic peptides exhibit besides antibiotic, antifungal and antiviral also anti-tumor activity. To enhance this natural antitumor properties the membrane-active part of Lactoferrin is taken as a parent peptide and will be further optimized in its activity and selectivity towards selected cancer cell lines. Although the exact killing mechanism on cancer cells is not understood, it is supposed that peptide-lipid interactions leading to membrane disruption are responsible for rapid killing by peptides, hindering the development of resistance which can occur with conventional chemotherapeutic drugs. Another big advantage is the strong selectivity for cancerous cells (over healthy cells). This is provided by the interaction of the cationic peptides with cancer cells that expose the negatively charged phospholipid phosphatidylserine (PS) in the outer leaflet of their plasma membranes which in healthy cells only comprise neutral lipids. Peptide optimization in respect of distribution of charges and hydrophobicity will be achieved by structure-activity relationship studies on model membranes followed by efficacy studies on cell cultures of cancer cells of diverse selected cancer types carrying the PS marker. The aim of the project is to develop novel highly potent agents against cancer cells acting rapidly by membrane lysis without any adverse reactions or formation of resistance.
Funder: Austrian Science Fund
Amount: €239,300
Funding type: grant
Funder scheme: Principal Investigator Projects
Start date: 2008-09-01
End date: 2012-08-31
Investigator: Dagmar Zweytick (lead)
Institutions: Austrian Academy of Sciences, University of Graz, Österreichische Akademie der Wissenschaften
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Funded outputs count: 3
Funder award ID: P20760
OpenAlex ID: G1663706835