APVV-15-0303

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Defense mechanisms of neoplastic cells against chemical stress       

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Principal investigator: Albert Breier
Principal investigator (IMPG SAS): Zdena Sulova

Duration: July 2016 – June 2020
Coordinating institution: Faculty of Chemical and Food Technology STU in Bratislava

Annotation:

Animal cells are disposing with large spectrum of defense mechanisms against damage induced by cytotoxic agents. These mechanisms are based on: i) ability of detoxification enzymes to modify the structure of cytotoxic agents; ii) ability of plasma membrane specialized transporters to eliminate the drugs from cell’s intracellular space; iii| changes in expression of cytotoxic agents target proteins; iv| changes in regulatory pathways responsible for initiation of programed cell death mechanisms as response of cell damage induced by cytotoxic agents. Initiation of these mechanisms in neoplastically altered tissue leads to multidrug resistance (MDR) development. Reduced cell sensitivity to large group of structurally unrelated anticancer drugs with different mechanisms of pharmacological action is feature typical for MDR. If MDR is developed in cancer tissue, it represents real obstacle of effective chemotherapy. MDR could develop in cells of alla types of solid malignant tumors and also in blood malignancies. MDR development could be considered as adaptation of neoplastic cells on previously applied chemotherapy cycles. However, MDR could be present in neoplastic cells of patients that were not treated by anticancer drugs. MDR in this case represents specific phenotype of neoplasticaly altered cells. Targeted research on this topic represents aim of this project.

Publications:
PubMed Pavlikova L, Seres M, Imrichova D, Hano M, Rusnak A, Zamorova M, Katrlik J, Breier A, Sulova Z. The expression of P-gp in leukemia cells is associated with cross-resistance to protein N-glycosylation inhibitor tunicamycin. Gen Physiol Biophys. 35 (2016) 497-510