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Drug repositioning for apoptosis induction and modulation of the autophagy process as a novel anticancer strategy
Serbia (IFMSA-Serbia) - University of Belgrade, Belgrade
Laboratory of immunology, Institute of Microbiology and immunology
Full prof. Vladimir Trajkovic, MD, PhD
Teaching assistant Marina Stamenković
Type of Research Project
- Basic science
What is the background of the project?
Acidity plays an important role in function and behavior of both healthy and cancer cells. In general, low pH is necessary for activation of enzymes in lysosomes, organelles involved in the digestion of various cell contents in the process called autophagy that provides energy for cell survival. On the other hand, one of the main features of cancer cells is acidic tumor microenvironment responsible for higher tumor invasiveness and resistance to pH dependent drugs. Since autophagy can be intensely activated and express cytoprotective effect in tumors it represents a novel target of anticancer therapy similarly as modulation of cell acidity. Drug repositioning involves researching of already existing drugs for the discovery of new indications and therapeutic approaches. In that aspect, proton pump inhibitors (PPI, commonly used for treating gastric disorders with high acid production) and drugs that decrease acidification of lysosomes (e.g. antimalarial drugs) can be used (repurposed) as anticancer agents.
What is the aim of the project?
Principal aim of this project is to explore potential anticancer effects of drugs that change cell acidity (e.g. PPI and antimalarial drugs) alone and in combination with pH sensitive drugs (e.g. vinca alkaloids etc.), their ability to induce apoptosis and their effect on main regulators of autophagic process (AMPK-AKT-mTOR axis) in various cancer cell lines
What techniques and methods are used?
Student will be introduced to the basics of cell culturing and maintenance of different commercially available cancer cell lines, perform viability tests such as MTT and crystal violet tests, clonogenic assay, preparation of samples for immunoblot analysis of various signaling molecules involved in the process of autophagy and apoptosis, real-time polymerase chain reaction for expression of main autophagy and apoptosis related genes and flow cytometry for determining cell death type, cell cycle, reactive oxygen species production etc.
What is the role of the student?
- The student will mainly observe
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
What are the tasks expected to be accomplished by the student?
Given the opportunity to learn (and according to the candidate’s capabilities and hers/his preference to take part in practical aspect) the basics of various techniques used in life science research such as cell culturing, viability testing, immunoblot, real-time polymerase chain reaction and flow cytometric analysis, the student is expected to be motivated and highly interested in laboratory work and basic science research. It is favorable that the student is able to work in groups, to search literature related to the project topic on public libraries and to have the initiative to discuss experiment results with mentor.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Candidate will be provided with preliminary readings in form of research papers, basic guidelines for techniques used in project and she/he will be guided through experiments with detail explanation of the experimental model. Certain topics such as flow cytometry will be also covered in the form of lectures or seminars.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
No specific skills are required for participation
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
- Stamenkovic M; Janjetovic K; Paunovic V; Ciric D; Kravic-Stevovic T; Trajkovic V. Comparative analysis of cell death mechanisms induced by lysosomal autophagy inhibitors. Eur J Pharmacol. 2019 Sep 15;859:172540.
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