TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Jadranin, Milka
AU  - Stanković, Tijana
AU  - Banković, Jasna
AU  - Stojković, Sonja
AU  - Chiourea, Maria
AU  - Aljančić, Ivana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Ruzdijic, Sabera
AU  - Gagos, Sarantis
AU  - Tanić, Nikola
AU  - Pešić, Milica
PY  - 2013
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1393
AB  - Multi-drug resistance (MDR) is a major obstacle to successful cancer treatment. Therefore, in vitro models are necessary for the investigation of the phenotypic changes provoked by cytotoxic agents and more importantly for preclinical testing of new anticancer drugs. We analyzed chromosomal, numerical, and structural changes after development of MDR, alterations in p53 and PTEN, single nucleotide polymorphisms (SNPs) in the mdr1 gene and corresponding protein expression of P-glycoprotein (P-gp) in three human MDR cancer cell lines: non-small cell lung carcinoma NCI-H460/R, colorectal carcinoma DLD1-TxR, and glioma U87-TxR. In addition, we explored how these molecular and phenotypic alterations influence the anticancer effect of new drugs. Cytogenetic analysis showed polyploidy reduction after development of MDR in U87-TxR. Losses of 6q in all resistant cancer cell lines and inactivation of p53 in U87-TxR and PTEN in DLD1-TxR were also revealed. Overexpression of P-gp was observed in all MDR cancer cell lines. We evaluated the anticancer activities and MDR reversal potential of Akt inhibitor GSK690693, Ras inhibitor Tipifarnib, and two P-gp inhibitors (jatrophane diterpenoids). Their effects vary due to the cell-type differences, existence of MDR phenotype, presence of mdr1 SNP, and tumor suppressors' alterations. Tipifarnib and jatrophane diterpenoids significantly sensitized MDR cancer cells to paclitaxel. In conclusion, investigated MDR cancer cells obtained new molecular and cytogenetic characteristics that may serve as potential clinical prognostic markers. In addition, these MDR cancer cell lines present a valuable model for preclinical evaluation of new anticancer agents.
PB  - Springer, New York
T2  - Cancer Chemotherapy and Pharmacology
T1  - Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing
VL  - 72
IS  - 3
SP  - 683
EP  - 697
DO  - 10.1007/s00280-013-2247-1
ER  - 

@article{
author = "Podolski-Renić, Ana and Jadranin, Milka and Stanković, Tijana and Banković, Jasna and Stojković, Sonja and Chiourea, Maria and Aljančić, Ivana and Vajs, Vlatka and Tešević, Vele and Ruzdijic, Sabera and Gagos, Sarantis and Tanić, Nikola and Pešić, Milica",
year = "2013",
abstract = "Multi-drug resistance (MDR) is a major obstacle to successful cancer treatment. Therefore, in vitro models are necessary for the investigation of the phenotypic changes provoked by cytotoxic agents and more importantly for preclinical testing of new anticancer drugs. We analyzed chromosomal, numerical, and structural changes after development of MDR, alterations in p53 and PTEN, single nucleotide polymorphisms (SNPs) in the mdr1 gene and corresponding protein expression of P-glycoprotein (P-gp) in three human MDR cancer cell lines: non-small cell lung carcinoma NCI-H460/R, colorectal carcinoma DLD1-TxR, and glioma U87-TxR. In addition, we explored how these molecular and phenotypic alterations influence the anticancer effect of new drugs. Cytogenetic analysis showed polyploidy reduction after development of MDR in U87-TxR. Losses of 6q in all resistant cancer cell lines and inactivation of p53 in U87-TxR and PTEN in DLD1-TxR were also revealed. Overexpression of P-gp was observed in all MDR cancer cell lines. We evaluated the anticancer activities and MDR reversal potential of Akt inhibitor GSK690693, Ras inhibitor Tipifarnib, and two P-gp inhibitors (jatrophane diterpenoids). Their effects vary due to the cell-type differences, existence of MDR phenotype, presence of mdr1 SNP, and tumor suppressors' alterations. Tipifarnib and jatrophane diterpenoids significantly sensitized MDR cancer cells to paclitaxel. In conclusion, investigated MDR cancer cells obtained new molecular and cytogenetic characteristics that may serve as potential clinical prognostic markers. In addition, these MDR cancer cell lines present a valuable model for preclinical evaluation of new anticancer agents.",
publisher = "Springer, New York",
journal = "Cancer Chemotherapy and Pharmacology",
title = "Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing",
volume = "72",
number = "3",
pages = "683-697",
doi = "10.1007/s00280-013-2247-1"
}

Podolski-Renić, A., Jadranin, M., Stanković, T., Banković, J., Stojković, S., Chiourea, M., Aljančić, I., Vajs, V., Tešević, V., Ruzdijic, S., Gagos, S., Tanić, N.,& Pešić, M.. (2013). Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing. in Cancer Chemotherapy and Pharmacology
Springer, New York., 72(3), 683-697.
https://doi.org/10.1007/s00280-013-2247-1

Podolski-Renić A, Jadranin M, Stanković T, Banković J, Stojković S, Chiourea M, Aljančić I, Vajs V, Tešević V, Ruzdijic S, Gagos S, Tanić N, Pešić M. Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing. in Cancer Chemotherapy and Pharmacology. 2013;72(3):683-697.
doi:10.1007/s00280-013-2247-1 .

Podolski-Renić, Ana, Jadranin, Milka, Stanković, Tijana, Banković, Jasna, Stojković, Sonja, Chiourea, Maria, Aljančić, Ivana, Vajs, Vlatka, Tešević, Vele, Ruzdijic, Sabera, Gagos, Sarantis, Tanić, Nikola, Pešić, Milica, "Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing" in Cancer Chemotherapy and Pharmacology, 72, no. 3 (2013):683-697,
https://doi.org/10.1007/s00280-013-2247-1 . .