TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Stanković, Tijana
AU  - Tsakovska, Ivanka
AU  - Pajeva, Ilza
AU  - Tuccinardi, Tiziano
AU  - Botta, Lorenzo
AU  - Schenone, Silvia
AU  - Pešić, Milica
PY  - 2021
UR  - https://www.mdpi.com/2072-6694/13/21/5308
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4631
AB  - Tyrosine kinase inhibitors (TKIs) often interact with the multidrug resistant (MDR) phenotype of cancer cells. In some cases, TKIs increase the susceptibility of MDR cancer cells to chemotherapy. As the overexpression of membrane transporter P‐glycoprotein (P‐gp) is the most com-mon alteration in MDR cancer cells, we investigated the effects of TKI pyrazolo[3,4‐d]pyrimidines on P‐gp inhibition in two cellular models comprising sensitive and corresponding MDR cancer cells (human non‐small cell lung carcinoma and colorectal adenocarcinoma). Tested TKIs showed collateral sensitivity by inducing stronger inhibition of MDR cancer cell line viability. Moreover, TKIs directly interacted with P‐gp and inhibited its ATPase activity. Their potential P‐gp binding site was proposed by molecular docking simulations. TKIs reversed resistance to doxorubicin and paclitaxel in a concentration‐dependent manner. The expression studies excluded the indirect effect of TKIs on P‐gp through regulation of its expression. A kinetics study showed that TKIs decreased P‐gp activity and this effect was sustained for seven days in both MDR models. Therefore, pyrazolo[3,4‐d]pyrimidines with potential for reversing P‐gp‐mediated MDR even in prolonged treatments can be considered a new therapeutic strategy for overcoming cancer MDR.
PB  - Basel: MDPI
T2  - Cancers
T1  - New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors
IS  - 21
VL  - 13
DO  - 10.3390/cancers13215308
SP  - 5308
ER  - 

@article{
author = "Podolski-Renić, Ana and Dinić, Jelena and Stanković, Tijana and Tsakovska, Ivanka and Pajeva, Ilza and Tuccinardi, Tiziano and Botta, Lorenzo and Schenone, Silvia and Pešić, Milica",
year = "2021",
abstract = "Tyrosine kinase inhibitors (TKIs) often interact with the multidrug resistant (MDR) phenotype of cancer cells. In some cases, TKIs increase the susceptibility of MDR cancer cells to chemotherapy. As the overexpression of membrane transporter P‐glycoprotein (P‐gp) is the most com-mon alteration in MDR cancer cells, we investigated the effects of TKI pyrazolo[3,4‐d]pyrimidines on P‐gp inhibition in two cellular models comprising sensitive and corresponding MDR cancer cells (human non‐small cell lung carcinoma and colorectal adenocarcinoma). Tested TKIs showed collateral sensitivity by inducing stronger inhibition of MDR cancer cell line viability. Moreover, TKIs directly interacted with P‐gp and inhibited its ATPase activity. Their potential P‐gp binding site was proposed by molecular docking simulations. TKIs reversed resistance to doxorubicin and paclitaxel in a concentration‐dependent manner. The expression studies excluded the indirect effect of TKIs on P‐gp through regulation of its expression. A kinetics study showed that TKIs decreased P‐gp activity and this effect was sustained for seven days in both MDR models. Therefore, pyrazolo[3,4‐d]pyrimidines with potential for reversing P‐gp‐mediated MDR even in prolonged treatments can be considered a new therapeutic strategy for overcoming cancer MDR.",
publisher = "Basel: MDPI",
journal = "Cancers",
title = "New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors",
number = "21",
volume = "13",
doi = "10.3390/cancers13215308",
pages = "5308"
}

Podolski-Renić, A., Dinić, J., Stanković, T., Tsakovska, I., Pajeva, I., Tuccinardi, T., Botta, L., Schenone, S.,& Pešić, M.. (2021). New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors. in Cancers
Basel: MDPI., 13(21), 5308.
https://doi.org/10.3390/cancers13215308

Podolski-Renić A, Dinić J, Stanković T, Tsakovska I, Pajeva I, Tuccinardi T, Botta L, Schenone S, Pešić M. New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors. in Cancers. 2021;13(21):5308.
doi:10.3390/cancers13215308 .

Podolski-Renić, Ana, Dinić, Jelena, Stanković, Tijana, Tsakovska, Ivanka, Pajeva, Ilza, Tuccinardi, Tiziano, Botta, Lorenzo, Schenone, Silvia, Pešić, Milica, "New therapeutic strategy for overcoming multidrug resistance in cancer cells with pyrazolo[3,4‐d]pyrimidine tyrosine kinase inhibitors" in Cancers, 13, no. 21 (2021):5308,
https://doi.org/10.3390/cancers13215308 . .