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 . .

TY  - JOUR
AU  - Aljančić, Ivana
AU  - Pešić, Milica
AU  - Milosavljević, Slobodan M.
AU  - Todorović, Nina
AU  - Jadranin, Milka
AU  - Miosavljevic, Goran
AU  - Povrenovic, Dragan
AU  - Banković, Jasna
AU  - Tanić, Nikola
AU  - Marković, Ivanka
AU  - Ruzdijic, Sabera
AU  - Vajs, Vlatka
AU  - Tešević, Vele
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1178
AB  - From the Montenegrin spurge Euphorbia dendroides, seven new diterpenoids [jatrophanes (1-6) and a tigliane (7)] were isolated and their structures elucidated by spectroscopic techniques. The biological activity of the new compounds was studied against four human cancer cell lines. The most effective jatrophane-type compound (2) and its structurally closely related derivative (1) were evaluated for their interactions with paclitaxel and doxorubicin using a multidrug-resistant cancer cell line. Both compounds exerted a strong reversal potential resulting from inhibition of P-glycoprotein transport.
PB  - Amer Chemical Soc, Washington
T2  - Journal of Natural Products
T1  - Isolation and Biological Evaluation of Jatrophane Diterpenoids from Euphorbia dendroides
VL  - 74
IS  - 7
SP  - 1613
EP  - 1620
DO  - 10.1021/np200241c
ER  - 

@article{
author = "Aljančić, Ivana and Pešić, Milica and Milosavljević, Slobodan M. and Todorović, Nina and Jadranin, Milka and Miosavljevic, Goran and Povrenovic, Dragan and Banković, Jasna and Tanić, Nikola and Marković, Ivanka and Ruzdijic, Sabera and Vajs, Vlatka and Tešević, Vele",
year = "2011",
abstract = "From the Montenegrin spurge Euphorbia dendroides, seven new diterpenoids [jatrophanes (1-6) and a tigliane (7)] were isolated and their structures elucidated by spectroscopic techniques. The biological activity of the new compounds was studied against four human cancer cell lines. The most effective jatrophane-type compound (2) and its structurally closely related derivative (1) were evaluated for their interactions with paclitaxel and doxorubicin using a multidrug-resistant cancer cell line. Both compounds exerted a strong reversal potential resulting from inhibition of P-glycoprotein transport.",
publisher = "Amer Chemical Soc, Washington",
journal = "Journal of Natural Products",
title = "Isolation and Biological Evaluation of Jatrophane Diterpenoids from Euphorbia dendroides",
volume = "74",
number = "7",
pages = "1613-1620",
doi = "10.1021/np200241c"
}

Aljančić, I., Pešić, M., Milosavljević, S. M., Todorović, N., Jadranin, M., Miosavljevic, G., Povrenovic, D., Banković, J., Tanić, N., Marković, I., Ruzdijic, S., Vajs, V.,& Tešević, V.. (2011). Isolation and Biological Evaluation of Jatrophane Diterpenoids from Euphorbia dendroides. in Journal of Natural Products
Amer Chemical Soc, Washington., 74(7), 1613-1620.
https://doi.org/10.1021/np200241c

Aljančić I, Pešić M, Milosavljević SM, Todorović N, Jadranin M, Miosavljevic G, Povrenovic D, Banković J, Tanić N, Marković I, Ruzdijic S, Vajs V, Tešević V. Isolation and Biological Evaluation of Jatrophane Diterpenoids from Euphorbia dendroides. in Journal of Natural Products. 2011;74(7):1613-1620.
doi:10.1021/np200241c .

Aljančić, Ivana, Pešić, Milica, Milosavljević, Slobodan M., Todorović, Nina, Jadranin, Milka, Miosavljevic, Goran, Povrenovic, Dragan, Banković, Jasna, Tanić, Nikola, Marković, Ivanka, Ruzdijic, Sabera, Vajs, Vlatka, Tešević, Vele, "Isolation and Biological Evaluation of Jatrophane Diterpenoids from Euphorbia dendroides" in Journal of Natural Products, 74, no. 7 (2011):1613-1620,
https://doi.org/10.1021/np200241c . .

TY  - JOUR
AU  - Pešić, Milica
AU  - Banković, Jasna
AU  - Aljančić, Ivana
AU  - Todorović, Nina
AU  - Jadranin, Milka
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Vučković, Ivan M.
AU  - Momčilović, Miljana
AU  - Marković, Ivanka
AU  - Tanić, Nikola
AU  - Ruzdijic, Sabera
PY  - 2011
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1233
AB  - Jatrophane diterpenes were shown to be inhibitors of P-glycoprotein (P-gp). There are also evidences on their microtubule-interacting activity in cancer cells. We evaluated new anti-cancer characteristics of two jatrophane type compounds from Euphorbia dendroides. For that purpose, the model system of sensitive non-small cell lung cancer cell line (NCI-H460) and its resistant counterpart (NCI-H460/R) was used. Although both jatrophanes showed inhibitory effect on cancer cell growth, they were non-toxic for peripheral blood mononuclear cells (PBMC). We examined their effects in combination with paclitaxel (PTX), a well-known mitotic spindle interacting chemotherapeutic. Jatrophanes overcome PTX resistance in concentration-dependent manner in MDR cancer cell line (NCI-H460/R). We observed that this synergistic effect is not caused merely by P-gp inhibition. In combination with PTX, jatrophanes induce cell killing and change cell cycle distribution leading to G2/M arrest. Furthermore, they exert an anti-angiogenic effect by decreasing the vascular endothelial growth factor (VEGF) secretion. The reduction of the level of mdr1 mRNA expression in sensitive cells, suggests that these compounds could not contribute to the development of resistance. In conclusion, present study provides a rational basis for the new cancer treatment approach with jatrophanes that are non-toxic to normal cells and have new favorable anti-cancer characteristics. (C) 2011 Elsevier Ltd. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Food and Chemical Toxicology
T1  - New anti-cancer characteristics of jatrophane diterpenes from Euphorbia dendroides
VL  - 49
IS  - 12
SP  - 3165
EP  - 3173
DO  - 10.1016/j.fct.2011.09.035
ER  - 

@article{
author = "Pešić, Milica and Banković, Jasna and Aljančić, Ivana and Todorović, Nina and Jadranin, Milka and Vajs, Vlatka and Tešević, Vele and Vučković, Ivan M. and Momčilović, Miljana and Marković, Ivanka and Tanić, Nikola and Ruzdijic, Sabera",
year = "2011",
abstract = "Jatrophane diterpenes were shown to be inhibitors of P-glycoprotein (P-gp). There are also evidences on their microtubule-interacting activity in cancer cells. We evaluated new anti-cancer characteristics of two jatrophane type compounds from Euphorbia dendroides. For that purpose, the model system of sensitive non-small cell lung cancer cell line (NCI-H460) and its resistant counterpart (NCI-H460/R) was used. Although both jatrophanes showed inhibitory effect on cancer cell growth, they were non-toxic for peripheral blood mononuclear cells (PBMC). We examined their effects in combination with paclitaxel (PTX), a well-known mitotic spindle interacting chemotherapeutic. Jatrophanes overcome PTX resistance in concentration-dependent manner in MDR cancer cell line (NCI-H460/R). We observed that this synergistic effect is not caused merely by P-gp inhibition. In combination with PTX, jatrophanes induce cell killing and change cell cycle distribution leading to G2/M arrest. Furthermore, they exert an anti-angiogenic effect by decreasing the vascular endothelial growth factor (VEGF) secretion. The reduction of the level of mdr1 mRNA expression in sensitive cells, suggests that these compounds could not contribute to the development of resistance. In conclusion, present study provides a rational basis for the new cancer treatment approach with jatrophanes that are non-toxic to normal cells and have new favorable anti-cancer characteristics. (C) 2011 Elsevier Ltd. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Food and Chemical Toxicology",
title = "New anti-cancer characteristics of jatrophane diterpenes from Euphorbia dendroides",
volume = "49",
number = "12",
pages = "3165-3173",
doi = "10.1016/j.fct.2011.09.035"
}

Pešić, M., Banković, J., Aljančić, I., Todorović, N., Jadranin, M., Vajs, V., Tešević, V., Vučković, I. M., Momčilović, M., Marković, I., Tanić, N.,& Ruzdijic, S.. (2011). New anti-cancer characteristics of jatrophane diterpenes from Euphorbia dendroides. in Food and Chemical Toxicology
Pergamon-Elsevier Science Ltd, Oxford., 49(12), 3165-3173.
https://doi.org/10.1016/j.fct.2011.09.035

Pešić M, Banković J, Aljančić I, Todorović N, Jadranin M, Vajs V, Tešević V, Vučković IM, Momčilović M, Marković I, Tanić N, Ruzdijic S. New anti-cancer characteristics of jatrophane diterpenes from Euphorbia dendroides. in Food and Chemical Toxicology. 2011;49(12):3165-3173.
doi:10.1016/j.fct.2011.09.035 .

Pešić, Milica, Banković, Jasna, Aljančić, Ivana, Todorović, Nina, Jadranin, Milka, Vajs, Vlatka, Tešević, Vele, Vučković, Ivan M., Momčilović, Miljana, Marković, Ivanka, Tanić, Nikola, Ruzdijic, Sabera, "New anti-cancer characteristics of jatrophane diterpenes from Euphorbia dendroides" in Food and Chemical Toxicology, 49, no. 12 (2011):3165-3173,
https://doi.org/10.1016/j.fct.2011.09.035 . .