The scientific board of CBs SAS evaluated as the 3rd most important result of 2018 in the application area the work of the authors V. Bohacova, M. Seres, L. Pavlikova, S. Kontar, M. Cagala, Z. Sulova, A. Breier:
“Research into the possibilities of efficiently chemotherapeutic treatment of leukemic cells with developed multi-drug resistance based on P-gp efflux activity”
We have shown that triorganocin derivatives, known as xenobiotic RXR nuclear receptor ligands, induce apoptosis of L1210 cells at submicromolar concentrations independent of
expression of P-gp. The significance of this result can be underlined by the fact that in applied and translational research associated with the rational development of anticancer drugs, there is an increasing interest in those that are unable to eliminate multidrug resistance-associated proteins from cells. It seems that such substances could also be tents (organotin derivatives) as they have a more pronounced effect on neoplastically transformed than on normal cells.
In cells overexpressing P-gp, it is difficult to use analytical methods based on measuring the retention and specific fluorescence of intracellular indicators, as these are often substrates
Pgp. This is also the case when measuring mitochondrial membrane potential with JC-1. Therefore, we have developed a rapid method based on specific inhibition of P-gp with tariquidar, which allows detection of mitochondrial membrane potential even in cells with high P-gp content. This method may find application in applied research associated with rapid detection of mitochondrial damage by cytotoxic agents even in neoplastic cells with developed multidrug resistance mediated by P-gp efflux activity.
Projects: APVV-14-0334, 15-0303, 15-0372, 15-0641, VEGA 2/0028/15, 2/0156/16, 2/0122/17, ITMS 26240220071, ITMS 26230120006.
Publications:
BOHACOVA, Viera – SERES, Mario – PAVLIKOVA, Lucia – KONTAR, Szilvia – CAGALA, Martin – BOBAL, Pavel – OTEVREL, Jan – BRTKO, Julius – SULOVA, Zdena – BREIER, Albert. Triorganotin derivatives induce cell death effects on L1210 leukemia cells at submicromolar concentration mainly of P-glycoprotein expression. In Molecules, 2018, vol. 23, iss. 5, art. no. 1053. (3,098 -IF2017). ISSN 1420-3049.
ELEFANTOVA, Katarina – LAKATOS, Boris – KUBICKOVA, Jana – SULOVA, Zdena – BREIER, Albert. Detection of the Mitochondrial Membrane Potential by Cationic Dye JC-1 in L1210 Cells with Massive Overexpression of the Plasma Membrane ABCB1 Drug Transporter. In the International Journal of Molecular Sciences, 2018, vol. 19, art. no. 1985. (3,687 – IF2017). ISSN 1422-0067.
