Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing
Samo za registrovane korisnike
2013
Autori
Podolski-Renic, AnaJadranin, Milka
Stankovic, Tijana
Bankovic, Jasna
Stojkovic, Sonja
Chiourea, Maria
Aljančić, Ivana
Vajs, Vlatka
Tešević, Vele
Ruzdijic, Sabera
Gagos, Sarantis
Tanic, Nikola
Pešić, Milica
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 al...l 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.
Ključne reči:
Multi-drug resistance / Cytogenetics / Loss of heterozygosity / P-glycoprotein / Anticancer agentsIzvor:
Cancer Chemotherapy and Pharmacology, 2013, 72, 3, 683-697Izdavač:
- Springer, New York
Finansiranje / projekti:
- Identifikacija molekularnih markera za predikciju progresije tumora, odgovora na terapiju i ishoda bolesti (RS-41031)
- Bioaktivni prirodni proizvodi samoniklih, gajenih i jestivih biljaka: određivanje struktura i aktivnosti (RS-172053)
- Cancer and Control of Genomic Integrity (CANGENIN) COST Action [BM0703]
DOI: 10.1007/s00280-013-2247-1
ISSN: 0344-5704
PubMed: 23934261
WoS: 000323653600020
Scopus: 2-s2.0-84883488322
Institucija/grupa
IHTMTY - JOUR AU - Podolski-Renic, Ana AU - Jadranin, Milka AU - Stankovic, Tijana AU - Bankovic, Jasna AU - Stojkovic, Sonja AU - Chiourea, Maria AU - Aljančić, Ivana AU - Vajs, Vlatka AU - Tešević, Vele AU - Ruzdijic, Sabera AU - Gagos, Sarantis AU - Tanic, Nikola AU - Pešić, Milica PY - 2013 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1176 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-Renic, Ana and Jadranin, Milka and Stankovic, Tijana and Bankovic, Jasna and Stojkovic, Sonja and Chiourea, Maria and Aljančić, Ivana and Vajs, Vlatka and Tešević, Vele and Ruzdijic, Sabera and Gagos, Sarantis and Tanic, 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-Renic, A., Jadranin, M., Stankovic, T., Bankovic, J., Stojkovic, S., Chiourea, M., Aljančić, I., Vajs, V., Tešević, V., Ruzdijic, S., Gagos, S., Tanic, 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-Renic A, Jadranin M, Stankovic T, Bankovic J, Stojkovic S, Chiourea M, Aljančić I, Vajs V, Tešević V, Ruzdijic S, Gagos S, Tanic 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-Renic, Ana, Jadranin, Milka, Stankovic, Tijana, Bankovic, Jasna, Stojkovic, Sonja, Chiourea, Maria, Aljančić, Ivana, Vajs, Vlatka, Tešević, Vele, Ruzdijic, Sabera, Gagos, Sarantis, Tanic, 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 . .