Study of autophagy induction of salycilanilide derivatives on glioma cells
In the treatment of central nervous system related gliomas, the emergence of chemoresistance is a major problem for which tumor stem cells are also responsible. Based on literature data and previous results of our research group, salicylanilide (2-hydroxy-N-phenylbenzamide) type compounds were identified which can eliminate tumor stem cells due to their autophagy and apoptosis inducing effect.
Our aim is to design and synthesize novel peptide carriers and to produce salicylanilide-peptide bioconjugates. During the mentoring period, the student acquires the basics of Western blot method and develops a test system which can be routinely used to examine the effect of novel conjugates on autophagy. During the experiments, glioma cells will be treated with peptides and cell lysates will be prepared. After gel electrophoresis of cell lysates, separated proteins will be blotted to PVBF membrane. The effect of the bioconjugates on autophagy will be detected with an antibody that binds to a specific autophagy marker. This method is suitable for monitoring changes in cellular gene expression via the changes in the ratio of autophagy related proteins. Consequently, the effect of different peptide carriers and binding types in the bioconjugates on the development of autophagy - important to tumor cell inhibition - can be compared. Based on our results, design of novel peptide carriers and the improvement of existing ones will become possible. The student will be able to optimize other types of Western blot-based techniques and these systems can be further used for the determination of structure-activity relationships in case of other bioconjugates.
Beáta Biri-Kovács, Lilla Horváth