TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Dinić, Jelena
AU  - Stanković, Tijana
AU  - Jovanović, Mirna
AU  - Ramović, Amra
AU  - Pustenko, Aleksandrs
AU  - Žalubovskis, Raivis
AU  - Pešić, Milica
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0928098719302751?dgcid=coauthor
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3441
AB  - New 6-triazolyl-substituted sulfocoumarins were described as potent inhibitors of the transmembrane human carbonic anhydrase isoforms, CAIX and CAXII. These membrane associated enzymes that maintain pH and CO2 homeostasis are involved in cancer progression, invasion, and resistance to therapy. Recently, it was shown that CAXII expression associates with the expression of P-glycoprotein in multidrug resistant cancer cells. CAXII regulates P-glycoprotein activity by maintaining high intracellular pHi. In this study, the activity of three new sulfocoumarins was evaluated in three sensitive and corresponding multidrug resistant cancer cell lines with increased P-glycoprotein expression (non-small cell lung carcinoma, colorectal carcinoma and glioblastoma). Compound 3 showed the highest potential for cancer cell growth inhibition in all tested cell lines. Flow cytometric analyses showed that compound 3 induced intracellular acidification, cell cycle arrest in G2/M phase and necrosis in non-small cell lung carcinoma cells. Compound 3 demonstrated irreversible, concentration- and time-dependent inhibition of P-glycoprotein activity in multidrug resistant non-small cell lung carcinoma cells. The suppression of P-glycoprotein activity was accompanied with increased P-glycoprotein expression suggesting a compensatory mechanism of multidrug resistant cancer cells. In addition, compound 3 was able to sensitize multidrug resistant non-small cell lung carcinoma cells to doxorubicin. Overall, results imply that compound 3 has multidrug resistance modulating effect through intracellular acidification and subsequent inhibition of P-glycoprotein activity.
T2  - European Journal of Pharmaceutical Sciences
T1  - Sulfocoumarins, specific carbonic anhydrase IX and XII inhibitors, interact with cancer multidrug resistant phenotype through pH regulation and reverse P-glycoprotein mediated resistance.
VL  - 138
DO  - 10.1016/j.ejps.2019.105012
SP  - 105012
ER  - 

@article{
author = "Podolski-Renić, Ana and Dinić, Jelena and Stanković, Tijana and Jovanović, Mirna and Ramović, Amra and Pustenko, Aleksandrs and Žalubovskis, Raivis and Pešić, Milica",
year = "2019",
abstract = "New 6-triazolyl-substituted sulfocoumarins were described as potent inhibitors of the transmembrane human carbonic anhydrase isoforms, CAIX and CAXII. These membrane associated enzymes that maintain pH and CO2 homeostasis are involved in cancer progression, invasion, and resistance to therapy. Recently, it was shown that CAXII expression associates with the expression of P-glycoprotein in multidrug resistant cancer cells. CAXII regulates P-glycoprotein activity by maintaining high intracellular pHi. In this study, the activity of three new sulfocoumarins was evaluated in three sensitive and corresponding multidrug resistant cancer cell lines with increased P-glycoprotein expression (non-small cell lung carcinoma, colorectal carcinoma and glioblastoma). Compound 3 showed the highest potential for cancer cell growth inhibition in all tested cell lines. Flow cytometric analyses showed that compound 3 induced intracellular acidification, cell cycle arrest in G2/M phase and necrosis in non-small cell lung carcinoma cells. Compound 3 demonstrated irreversible, concentration- and time-dependent inhibition of P-glycoprotein activity in multidrug resistant non-small cell lung carcinoma cells. The suppression of P-glycoprotein activity was accompanied with increased P-glycoprotein expression suggesting a compensatory mechanism of multidrug resistant cancer cells. In addition, compound 3 was able to sensitize multidrug resistant non-small cell lung carcinoma cells to doxorubicin. Overall, results imply that compound 3 has multidrug resistance modulating effect through intracellular acidification and subsequent inhibition of P-glycoprotein activity.",
journal = "European Journal of Pharmaceutical Sciences",
title = "Sulfocoumarins, specific carbonic anhydrase IX and XII inhibitors, interact with cancer multidrug resistant phenotype through pH regulation and reverse P-glycoprotein mediated resistance.",
volume = "138",
doi = "10.1016/j.ejps.2019.105012",
pages = "105012"
}

Podolski-Renić, A., Dinić, J., Stanković, T., Jovanović, M., Ramović, A., Pustenko, A., Žalubovskis, R.,& Pešić, M.. (2019). Sulfocoumarins, specific carbonic anhydrase IX and XII inhibitors, interact with cancer multidrug resistant phenotype through pH regulation and reverse P-glycoprotein mediated resistance.. in European Journal of Pharmaceutical Sciences, 138, 105012.
https://doi.org/10.1016/j.ejps.2019.105012

Podolski-Renić A, Dinić J, Stanković T, Jovanović M, Ramović A, Pustenko A, Žalubovskis R, Pešić M. Sulfocoumarins, specific carbonic anhydrase IX and XII inhibitors, interact with cancer multidrug resistant phenotype through pH regulation and reverse P-glycoprotein mediated resistance.. in European Journal of Pharmaceutical Sciences. 2019;138:105012.
doi:10.1016/j.ejps.2019.105012 .

Podolski-Renić, Ana, Dinić, Jelena, Stanković, Tijana, Jovanović, Mirna, Ramović, Amra, Pustenko, Aleksandrs, Žalubovskis, Raivis, Pešić, Milica, "Sulfocoumarins, specific carbonic anhydrase IX and XII inhibitors, interact with cancer multidrug resistant phenotype through pH regulation and reverse P-glycoprotein mediated resistance." in European Journal of Pharmaceutical Sciences, 138 (2019):105012,
https://doi.org/10.1016/j.ejps.2019.105012 . .