TY  - JOUR
AU  - Milošević, Zorica
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Tsimplouli, Chrisiida
AU  - Sereti, Evangelia
AU  - Dragoj, Miodrag
AU  - Paunović, Verica
AU  - Milovanović, Zorka
AU  - Nešović, Marija
AU  - Tanić, Nikola
AU  - Dimas, Kostantinos
AU  - Pešić, Milica
PY  - 2018
UR  - https://link.springer.com/article/10.1007%2Fs13402-018-0380-x
UR  - https://radar.ibiss.bg.ac.rs/123456789/3887
AB  - Purpose: Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate.
Methods: Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies.
Results: Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth.
Conclusions: Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.
PB  - Basel : Springer Nature
T2  - Cellular Oncology (Dordrecht)
T1  - Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma
VL  - 41
DO  - 10.1007/s13402-018-0380-x
SP  - 409
EP  - 426
ER  - 

@article{
author = "Milošević, Zorica and Banković, Jasna and Dinić, Jelena and Tsimplouli, Chrisiida and Sereti, Evangelia and Dragoj, Miodrag and Paunović, Verica and Milovanović, Zorka and Nešović, Marija and Tanić, Nikola and Dimas, Kostantinos and Pešić, Milica",
year = "2018",
abstract = "Purpose: Anaplastic thyroid carcinoma (ATC) is an aggressive, chemo-resistant malignancy. Chemo-resistance is often associated with changes in activity of the RAS/MAPK/ERK and PI3K/AKT/mTOR pathways and/or a high expression of ATP binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). To assess the therapeutic efficacy in ATC of a combination of the dual mTOR kinase inhibitor vistusertib (AZD2014) and paclitaxel (PTX), we generated a new cell line (Rho-) via the selection of human thyroid carcinoma 8505C cells that exhibit a low accumulation of rhodamine 123, which serves as a P-gp and BCRP substrate.
Methods: Immunohistochemistry was used for P-gp and BCRP expression analyses in primary ATC patient samples. Spheroid formation and immunodeficient NSG mice were used for performing in vitro and in vivo tumorigenicity assays, respectively. MTT, flow-cytometry, fluorescent microscopy, cell death and proliferation assays, as well as migration, invasion and gelatin degradation assays, were used to assess the potential of AZD2014 to enhance the effects of PTX. ATC xenografts in SCID mice were used for evaluating in vivo treatment efficacies.
Results: Rho- cells were found to be 10-fold more resistant to PTX than 8505C cells and, in addition, to be more tumorigenic. We also found that AZD2014 sensitized Rho- cells to PTX by inhibiting proliferation and by inducing autophagy. The combined use of AZD2014 and PTX efficiently inhibited in vitro ATC cell migration and invasion. Subsequent in vivo xenograft studies indicated that the AZD2014 and PTX combination effectively suppressed ATC tumor growth.
Conclusions: Our data support results from recent phase I clinical trials using combinations of AZD2014 and PTX for the treatment of solid tumors. Such combinations may also be employed for the design of novel targeted ATC treatment strategies.",
publisher = "Basel : Springer Nature",
journal = "Cellular Oncology (Dordrecht)",
title = "Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma",
volume = "41",
doi = "10.1007/s13402-018-0380-x",
pages = "409-426"
}

Milošević, Z., Banković, J., Dinić, J., Tsimplouli, C., Sereti, E., Dragoj, M., Paunović, V., Milovanović, Z., Nešović, M., Tanić, N., Dimas, K.,& Pešić, M.. (2018). Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma. in Cellular Oncology (Dordrecht)
Basel : Springer Nature., 41, 409-426.
https://doi.org/10.1007/s13402-018-0380-x

Milošević Z, Banković J, Dinić J, Tsimplouli C, Sereti E, Dragoj M, Paunović V, Milovanović Z, Nešović M, Tanić N, Dimas K, Pešić M. Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma. in Cellular Oncology (Dordrecht). 2018;41:409-426.
doi:10.1007/s13402-018-0380-x .

Milošević, Zorica, Banković, Jasna, Dinić, Jelena, Tsimplouli, Chrisiida, Sereti, Evangelia, Dragoj, Miodrag, Paunović, Verica, Milovanović, Zorka, Nešović, Marija, Tanić, Nikola, Dimas, Kostantinos, Pešić, Milica, "Potential of the dual mTOR kinase inhibitor AZD2014 to overcome paclitaxel resistance in anaplastic thyroid carcinoma" in Cellular Oncology (Dordrecht), 41 (2018):409-426,
https://doi.org/10.1007/s13402-018-0380-x . .

TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Ríos-Luci, Carla
AU  - Fernandes, Miguel X.
AU  - Ortega, Nuria
AU  - Kovačević-Grujičić, Nataša
AU  - Martín, Víctor S.
AU  - Padrón, José M.
AU  - Pešić, Milica
PY  - 2017
UR  - https://www.sciencedirect.com/science/article/abs/pii/S0928098717302397
UR  - https://radar.ibiss.bg.ac.rs/123456789/3873
AB  - The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.
PB  - Amsterdam: Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells
VL  - 105
DO  - 10.1016/j.ejps.2017.05.011
SP  - 159
EP  - 168
ER  - 

@article{
author = "Podolski-Renić, Ana and Banković, Jasna and Dinić, Jelena and Ríos-Luci, Carla and Fernandes, Miguel X. and Ortega, Nuria and Kovačević-Grujičić, Nataša and Martín, Víctor S. and Padrón, José M. and Pešić, Milica",
year = "2017",
abstract = "The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.",
publisher = "Amsterdam: Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells",
volume = "105",
doi = "10.1016/j.ejps.2017.05.011",
pages = "159-168"
}

Podolski-Renić, A., Banković, J., Dinić, J., Ríos-Luci, C., Fernandes, M. X., Ortega, N., Kovačević-Grujičić, N., Martín, V. S., Padrón, J. M.,& Pešić, M.. (2017). DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences
Amsterdam: Elsevier., 105, 159-168.
https://doi.org/10.1016/j.ejps.2017.05.011

Podolski-Renić A, Banković J, Dinić J, Ríos-Luci C, Fernandes MX, Ortega N, Kovačević-Grujičić N, Martín VS, Padrón JM, Pešić M. DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences. 2017;105:159-168.
doi:10.1016/j.ejps.2017.05.011 .

Podolski-Renić, Ana, Banković, Jasna, Dinić, Jelena, Ríos-Luci, Carla, Fernandes, Miguel X., Ortega, Nuria, Kovačević-Grujičić, Nataša, Martín, Víctor S., Padrón, José M., Pešić, Milica, "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells" in European Journal of Pharmaceutical Sciences, 105 (2017):159-168,
https://doi.org/10.1016/j.ejps.2017.05.011 . .

TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Banković, Jasna
AU  - Dinić, Jelena
AU  - Ríos-Luci, Carla
AU  - Fernandes, Miguel X.
AU  - Ortega, Nuria
AU  - Kovačević-Grujičić, Nataša
AU  - Martín, Víctor S.
AU  - Padrón, José M.
AU  - Pešić, Milica
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0928098717302397
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2762
AB  - The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.
T2  - European Journal of Pharmaceutical Sciences
T1  - DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells
VL  - 105
DO  - 10.1016/j.ejps.2017.05.011
SP  - 159
EP  - 168
ER  - 

@article{
author = "Podolski-Renić, Ana and Banković, Jasna and Dinić, Jelena and Ríos-Luci, Carla and Fernandes, Miguel X. and Ortega, Nuria and Kovačević-Grujičić, Nataša and Martín, Víctor S. and Padrón, José M. and Pešić, Milica",
year = "2017",
abstract = "The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.",
journal = "European Journal of Pharmaceutical Sciences",
title = "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells",
volume = "105",
doi = "10.1016/j.ejps.2017.05.011",
pages = "159-168"
}

Podolski-Renić, A., Banković, J., Dinić, J., Ríos-Luci, C., Fernandes, M. X., Ortega, N., Kovačević-Grujičić, N., Martín, V. S., Padrón, J. M.,& Pešić, M.. (2017). DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences, 105, 159-168.
https://doi.org/10.1016/j.ejps.2017.05.011

Podolski-Renić A, Banković J, Dinić J, Ríos-Luci C, Fernandes MX, Ortega N, Kovačević-Grujičić N, Martín VS, Padrón JM, Pešić M. DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells. in European Journal of Pharmaceutical Sciences. 2017;105:159-168.
doi:10.1016/j.ejps.2017.05.011 .

Podolski-Renić, Ana, Banković, Jasna, Dinić, Jelena, Ríos-Luci, Carla, Fernandes, Miguel X., Ortega, Nuria, Kovačević-Grujičić, Nataša, Martín, Víctor S., Padrón, José M., Pešić, Milica, "DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells" in European Journal of Pharmaceutical Sciences, 105 (2017):159-168,
https://doi.org/10.1016/j.ejps.2017.05.011 . .

TY  - JOUR
AU  - Podolski-Renić, Ana
AU  - Milošević, Zorica
AU  - Dinić, Jelena
AU  - Stanković, Tijana
AU  - Banković, Jasna Z.
AU  - Pešić, Milica
PY  - 2016
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4051
AB  - Cancer-initiating cells referred to as cancer stem cells (CSCs) retain the essential property of self-renewal and protection. The protective mechanisms enable tumour regrowth even after the application of chemotherapy that was believed to be successful. Among the protective mechanisms of CSCs, the overexpression of ATP binding cassette (ABC) membrane transporters is highly important. ABC transporters involved in the development of cancer multidrug resistance (MDR) such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are considered as particular features of CSCs. They provide a shield for CSCs and protect them from the adverse effects of chemotherapeutics. Hence, combating MDR would be one of the strategies for the elimination of CSCs. In order to investigate this phenomenon many model systems comprising MDR cancer cells have been established. Some of them were developed by a selection process through exposure to various anticancer drugs, others by transfection of genes for ABC transporters, while some were obtained by sorting the side population considered to possess stemness and resistant phenotypes. Herein we review the potential of cancer MDR models for studying CSCs because gaining a better insight into the mechanisms of CSC resistance to chemotherapy may lead to the discovery of new therapeutic targets and the development of better anticancer strategies.
PB  - The Royal Society of Chemistry
T2  - MedChemComm
T1  - Mutual regulation and targeting of multidrug resistance and cancer stem phenotype
IS  - 12
VL  - 7
DO  - 10.1039/C6MD00391E
SP  - 2265
EP  - 2281
ER  - 

@article{
author = "Podolski-Renić, Ana and Milošević, Zorica and Dinić, Jelena and Stanković, Tijana and Banković, Jasna Z. and Pešić, Milica",
year = "2016",
abstract = "Cancer-initiating cells referred to as cancer stem cells (CSCs) retain the essential property of self-renewal and protection. The protective mechanisms enable tumour regrowth even after the application of chemotherapy that was believed to be successful. Among the protective mechanisms of CSCs, the overexpression of ATP binding cassette (ABC) membrane transporters is highly important. ABC transporters involved in the development of cancer multidrug resistance (MDR) such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are considered as particular features of CSCs. They provide a shield for CSCs and protect them from the adverse effects of chemotherapeutics. Hence, combating MDR would be one of the strategies for the elimination of CSCs. In order to investigate this phenomenon many model systems comprising MDR cancer cells have been established. Some of them were developed by a selection process through exposure to various anticancer drugs, others by transfection of genes for ABC transporters, while some were obtained by sorting the side population considered to possess stemness and resistant phenotypes. Herein we review the potential of cancer MDR models for studying CSCs because gaining a better insight into the mechanisms of CSC resistance to chemotherapy may lead to the discovery of new therapeutic targets and the development of better anticancer strategies.",
publisher = "The Royal Society of Chemistry",
journal = "MedChemComm",
title = "Mutual regulation and targeting of multidrug resistance and cancer stem phenotype",
number = "12",
volume = "7",
doi = "10.1039/C6MD00391E",
pages = "2265-2281"
}

Podolski-Renić, A., Milošević, Z., Dinić, J., Stanković, T., Banković, J. Z.,& Pešić, M.. (2016). Mutual regulation and targeting of multidrug resistance and cancer stem phenotype. in MedChemComm
The Royal Society of Chemistry., 7(12), 2265-2281.
https://doi.org/10.1039/C6MD00391E

Podolski-Renić A, Milošević Z, Dinić J, Stanković T, Banković JZ, Pešić M. Mutual regulation and targeting of multidrug resistance and cancer stem phenotype. in MedChemComm. 2016;7(12):2265-2281.
doi:10.1039/C6MD00391E .

Podolski-Renić, Ana, Milošević, Zorica, Dinić, Jelena, Stanković, Tijana, Banković, Jasna Z., Pešić, Milica, "Mutual regulation and targeting of multidrug resistance and cancer stem phenotype" in MedChemComm, 7, no. 12 (2016):2265-2281,
https://doi.org/10.1039/C6MD00391E . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Podolski-Renić, Ana
AU  - Stanković, Tijana
AU  - Banković, Jasna
AU  - Pešić, Milica
PY  - 2015
UR  - https://www.eurekaselect.com/135471/article
UR  - https://radar.ibiss.bg.ac.rs/123456789/3882
AB  - Resistance to chemotherapeautic drugs is one of the main obstacles to effective cancer treatment. Multidrug resistance (MDR) is defined as resistance to structurally and/or functionally unrelated drugs, and has been extensively investigated for the last three decades. There are two types of MDR: intrinsic and acquired. Tumor microenvironment selection pressure leads to the development of intrinsic MDR, while acquired resistance is a consequence of the administered chemotherapy. A central issue in chemotherapy failure is the existence of heterogeneous populations of cancer cells within one patient and patient-to-patient variability within each type of cancer.
Numerous genes and pathways contribute to the development of MDR in cancer. Point mutations, gene amplification or other genetic or epigenetic changes all affect biological functions and may lead to the occurrence of MDR phenotype. Similar to the characteristics of cancerogenesis, the main features of MDR include abnormal tumor vasculature, regions of hypoxia, aerobic glycolysis, and a lower susceptibility to apoptosis. In order to achieve a lethal effect on cancer cells, drugs need to reach their intracellular target molecules. The overexpression of the efflux transporter P-glycoprotein (P-gp) in MDR cancer cells leads to decreased uptake of the drug and intracellular drug accumulation, minimising drug-target interactions.
New agents being or inspired by natural products that sucessfully target these mechanisms are the main subject of this review. Two key approaches in combating MDR in cancer are discussed (i) finding agents that preserve citotoxicity toward MDR cancer cells; (ii) developing compounds that restore the cytotoxic activity of classic anticancer drugs.
PB  - Sharjah: Bentham Science Publishers
T2  - Current Pharmaceutical Design
T1  - New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer
IS  - 38
VL  - 21
DO  - 10.2174/1381612821666151002113546
SP  - 5589
EP  - 5604
ER  - 

@article{
author = "Dinić, Jelena and Podolski-Renić, Ana and Stanković, Tijana and Banković, Jasna and Pešić, Milica",
year = "2015",
abstract = "Resistance to chemotherapeautic drugs is one of the main obstacles to effective cancer treatment. Multidrug resistance (MDR) is defined as resistance to structurally and/or functionally unrelated drugs, and has been extensively investigated for the last three decades. There are two types of MDR: intrinsic and acquired. Tumor microenvironment selection pressure leads to the development of intrinsic MDR, while acquired resistance is a consequence of the administered chemotherapy. A central issue in chemotherapy failure is the existence of heterogeneous populations of cancer cells within one patient and patient-to-patient variability within each type of cancer.
Numerous genes and pathways contribute to the development of MDR in cancer. Point mutations, gene amplification or other genetic or epigenetic changes all affect biological functions and may lead to the occurrence of MDR phenotype. Similar to the characteristics of cancerogenesis, the main features of MDR include abnormal tumor vasculature, regions of hypoxia, aerobic glycolysis, and a lower susceptibility to apoptosis. In order to achieve a lethal effect on cancer cells, drugs need to reach their intracellular target molecules. The overexpression of the efflux transporter P-glycoprotein (P-gp) in MDR cancer cells leads to decreased uptake of the drug and intracellular drug accumulation, minimising drug-target interactions.
New agents being or inspired by natural products that sucessfully target these mechanisms are the main subject of this review. Two key approaches in combating MDR in cancer are discussed (i) finding agents that preserve citotoxicity toward MDR cancer cells; (ii) developing compounds that restore the cytotoxic activity of classic anticancer drugs.",
publisher = "Sharjah: Bentham Science Publishers",
journal = "Current Pharmaceutical Design",
title = "New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer",
number = "38",
volume = "21",
doi = "10.2174/1381612821666151002113546",
pages = "5589-5604"
}

Dinić, J., Podolski-Renić, A., Stanković, T., Banković, J.,& Pešić, M.. (2015). New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer. in Current Pharmaceutical Design
Sharjah: Bentham Science Publishers., 21(38), 5589-5604.
https://doi.org/10.2174/1381612821666151002113546

Dinić J, Podolski-Renić A, Stanković T, Banković J, Pešić M. New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer. in Current Pharmaceutical Design. 2015;21(38):5589-5604.
doi:10.2174/1381612821666151002113546 .

Dinić, Jelena, Podolski-Renić, Ana, Stanković, Tijana, Banković, Jasna, Pešić, Milica, "New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer" in Current Pharmaceutical Design, 21, no. 38 (2015):5589-5604,
https://doi.org/10.2174/1381612821666151002113546 . .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Podolski-Renić, Ana
AU  - Stankovic, Tijana
AU  - Banković, Jasna Z.
AU  - Pešić, Milica
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2041
AB  - Resistance to chemotherapeautic drugs is one of the main obstacles to
   effective cancer treatment. Multidrug resistance (MDR) is defined as
   resistance to structurally and/or functionally unrelated drugs, and has
   been extensively investigated for the last three decades. There are two
   types of MDR: intrinsic and acquired. Tumor microenvironment selection
   pressure leads to the development of intrinsic MDR, while acquired
   resistance is a consequence of the administered chemotherapy. A central
   issue in chemotherapy failure is the existence of heterogeneous
   populations of cancer cells within one patient and patient-to-patient
   variability within each type of cancer.
   Numerous genes and pathways contribute to the development of MDR in
   cancer. Point mutations, gene amplification or other genetic or
   epigenetic changes all affect biological functions and may lead to the
   occurrence of MDR phenotype. Similar to the characteristics of
   cancerogenesis, the main features of MDR include abnormal tumor
   vasculature, regions of hypoxia, aerobic glycolysis, and a lower
   susceptibility to apoptosis. In order to achieve a lethal effect on
   cancer cells, drugs need to reach their intracellular target molecules.
   The overexpression of the efflux transporter P-glycoprotein (P-gp) in
   MDR cancer cells leads to decreased uptake of the drug and intracellular
   drug accumulation, minimising drug-target interactions.
   New agents being or inspired by natural products that sucessfully target
   these mechanisms are the main subject of this review. Two key approaches
   in combating MDR in cancer are discussed (i) finding agents that
   preserve citotoxicity toward MDR cancer cells; (ii) developing compounds
   that restore the cytotoxic activity of classic anticancer drugs.
T2  - Current Pharmaceutical Design
T1  - New Approaches With Natural Product Drugs for Overcoming Multidrug
 Resistance in Cancer
IS  - 38
VL  - 21
DO  - 10.2174/1381612821666151002113546
SP  - 5589
EP  - 5604
ER  - 

@article{
author = "Dinić, Jelena and Podolski-Renić, Ana and Stankovic, Tijana and Banković, Jasna Z. and Pešić, Milica",
year = "2015",
abstract = "Resistance to chemotherapeautic drugs is one of the main obstacles to
   effective cancer treatment. Multidrug resistance (MDR) is defined as
   resistance to structurally and/or functionally unrelated drugs, and has
   been extensively investigated for the last three decades. There are two
   types of MDR: intrinsic and acquired. Tumor microenvironment selection
   pressure leads to the development of intrinsic MDR, while acquired
   resistance is a consequence of the administered chemotherapy. A central
   issue in chemotherapy failure is the existence of heterogeneous
   populations of cancer cells within one patient and patient-to-patient
   variability within each type of cancer.
   Numerous genes and pathways contribute to the development of MDR in
   cancer. Point mutations, gene amplification or other genetic or
   epigenetic changes all affect biological functions and may lead to the
   occurrence of MDR phenotype. Similar to the characteristics of
   cancerogenesis, the main features of MDR include abnormal tumor
   vasculature, regions of hypoxia, aerobic glycolysis, and a lower
   susceptibility to apoptosis. In order to achieve a lethal effect on
   cancer cells, drugs need to reach their intracellular target molecules.
   The overexpression of the efflux transporter P-glycoprotein (P-gp) in
   MDR cancer cells leads to decreased uptake of the drug and intracellular
   drug accumulation, minimising drug-target interactions.
   New agents being or inspired by natural products that sucessfully target
   these mechanisms are the main subject of this review. Two key approaches
   in combating MDR in cancer are discussed (i) finding agents that
   preserve citotoxicity toward MDR cancer cells; (ii) developing compounds
   that restore the cytotoxic activity of classic anticancer drugs.",
journal = "Current Pharmaceutical Design",
title = "New Approaches With Natural Product Drugs for Overcoming Multidrug
 Resistance in Cancer",
number = "38",
volume = "21",
doi = "10.2174/1381612821666151002113546",
pages = "5589-5604"
}

Dinić, J., Podolski-Renić, A., Stankovic, T., Banković, J. Z.,& Pešić, M.. (2015). New Approaches With Natural Product Drugs for Overcoming Multidrug
 Resistance in Cancer. in Current Pharmaceutical Design, 21(38), 5589-5604.
https://doi.org/10.2174/1381612821666151002113546

Dinić J, Podolski-Renić A, Stankovic T, Banković JZ, Pešić M. New Approaches With Natural Product Drugs for Overcoming Multidrug
 Resistance in Cancer. in Current Pharmaceutical Design. 2015;21(38):5589-5604.
doi:10.2174/1381612821666151002113546 .

Dinić, Jelena, Podolski-Renić, Ana, Stankovic, Tijana, Banković, Jasna Z., Pešić, Milica, "New Approaches With Natural Product Drugs for Overcoming Multidrug
 Resistance in Cancer" in Current Pharmaceutical Design, 21, no. 38 (2015):5589-5604,
https://doi.org/10.2174/1381612821666151002113546 . .

TY  - JOUR
AU  - Mori, Mattia
AU  - Vignaroli, Giulia
AU  - Cau, Ylenia
AU  - Dinić, Jelena
AU  - Hill, Richard
AU  - Rossi, Matteo
AU  - Colecchia, David
AU  - Pešić, Milica
AU  - Link, Wolfgang
AU  - Chiariello, Mario
AU  - Ottmann, Christian
AU  - Botta, Maurizio
PY  - 2014
UR  - https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/cmdc.201400044
UR  - https://radar.ibiss.bg.ac.rs/123456789/3886
AB  - 14-3-3 is a family of highly conserved adapter proteins that is attracting much interest among medicinal chemists. Small-molecule inhibitors of 14-3-3 protein-protein interactions (PPIs) are in high demand, both as tools to increase our understanding of 14-3-3 actions in human diseases and as leads to develop innovative therapeutic agents. Herein we present the discovery of novel 14-3-3 PPI inhibitors through a multidisciplinary strategy combining molecular modeling, organic synthesis, image-based high-content analysis of reporter cells, and in vitro assays using cancer cells. Notably, the two most active compounds promoted the translocation of c-Abl and FOXO pro-apoptotic factors into the nucleus and sensitized multidrug-resistant cancer cells to apoptotic inducers such as doxorubicin and the pan-Akt inhibitor GSK690693, thus becoming valuable lead candidates for further optimization. Our results emphasize the possible role of 14-3-3 PPI inhibitors in anticancer combination therapies.
PB  - Weinheim : Wiley-VCH
T2  - ChemMedChem
T1  - Discovery of 14‐3‐3 Protein–Protein Interaction Inhibitors that Sensitize Multidrug‐Resistant Cancer Cells to Doxorubicin and the Akt Inhibitor GSK690693
IS  - 5
VL  - 9
DO  - 10.1002/cmdc.201400044
SP  - 973
EP  - 983
ER  - 

@article{
author = "Mori, Mattia and Vignaroli, Giulia and Cau, Ylenia and Dinić, Jelena and Hill, Richard and Rossi, Matteo and Colecchia, David and Pešić, Milica and Link, Wolfgang and Chiariello, Mario and Ottmann, Christian and Botta, Maurizio",
year = "2014",
abstract = "14-3-3 is a family of highly conserved adapter proteins that is attracting much interest among medicinal chemists. Small-molecule inhibitors of 14-3-3 protein-protein interactions (PPIs) are in high demand, both as tools to increase our understanding of 14-3-3 actions in human diseases and as leads to develop innovative therapeutic agents. Herein we present the discovery of novel 14-3-3 PPI inhibitors through a multidisciplinary strategy combining molecular modeling, organic synthesis, image-based high-content analysis of reporter cells, and in vitro assays using cancer cells. Notably, the two most active compounds promoted the translocation of c-Abl and FOXO pro-apoptotic factors into the nucleus and sensitized multidrug-resistant cancer cells to apoptotic inducers such as doxorubicin and the pan-Akt inhibitor GSK690693, thus becoming valuable lead candidates for further optimization. Our results emphasize the possible role of 14-3-3 PPI inhibitors in anticancer combination therapies.",
publisher = "Weinheim : Wiley-VCH",
journal = "ChemMedChem",
title = "Discovery of 14‐3‐3 Protein–Protein Interaction Inhibitors that Sensitize Multidrug‐Resistant Cancer Cells to Doxorubicin and the Akt Inhibitor GSK690693",
number = "5",
volume = "9",
doi = "10.1002/cmdc.201400044",
pages = "973-983"
}

Mori, M., Vignaroli, G., Cau, Y., Dinić, J., Hill, R., Rossi, M., Colecchia, D., Pešić, M., Link, W., Chiariello, M., Ottmann, C.,& Botta, M.. (2014). Discovery of 14‐3‐3 Protein–Protein Interaction Inhibitors that Sensitize Multidrug‐Resistant Cancer Cells to Doxorubicin and the Akt Inhibitor GSK690693. in ChemMedChem
Weinheim : Wiley-VCH., 9(5), 973-983.
https://doi.org/10.1002/cmdc.201400044

Mori M, Vignaroli G, Cau Y, Dinić J, Hill R, Rossi M, Colecchia D, Pešić M, Link W, Chiariello M, Ottmann C, Botta M. Discovery of 14‐3‐3 Protein–Protein Interaction Inhibitors that Sensitize Multidrug‐Resistant Cancer Cells to Doxorubicin and the Akt Inhibitor GSK690693. in ChemMedChem. 2014;9(5):973-983.
doi:10.1002/cmdc.201400044 .

Mori, Mattia, Vignaroli, Giulia, Cau, Ylenia, Dinić, Jelena, Hill, Richard, Rossi, Matteo, Colecchia, David, Pešić, Milica, Link, Wolfgang, Chiariello, Mario, Ottmann, Christian, Botta, Maurizio, "Discovery of 14‐3‐3 Protein–Protein Interaction Inhibitors that Sensitize Multidrug‐Resistant Cancer Cells to Doxorubicin and the Akt Inhibitor GSK690693" in ChemMedChem, 9, no. 5 (2014):973-983,
https://doi.org/10.1002/cmdc.201400044 . .

TY  - JOUR
AU  - Mori, Mattia
AU  - Vignaroli, Giulia
AU  - Cau, Ylenia
AU  - Dinić, Jelena
AU  - Hill, Richard
AU  - Rossi, Matteo
AU  - Colecchia, David
AU  - Pešić, Milica
AU  - Link, Wolfgang
AU  - Chiariello, Mario
AU  - Ottmann, Christian
AU  - Botta, Maurizio
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2215
AB  - 14-3-3 is a family of highly conserved adapter proteins that is
   attracting much interest among medicinal chemists. Small-molecule
   inhibitors of 14-3-3 protein-protein interactions (PPIs) are in high
   demand, both as tools to increase our understanding of 14-3-3 actions in
   human diseases and as leads to develop innovative therapeutic agents.
   Herein we present the discovery of novel 14-3-3 PPI inhibitors through a
   multidisciplinary strategy combining molecular modeling, organic
   synthesis, image-based high-content analysis of reporter cells, and in
   vitro assays using cancer cells. Notably, the two most active compounds
   promoted the translocation of c-Abl and FOXO pro-apoptotic factors into
   the nucleus and sensitized multidrug-resistant cancer cells to apoptotic
   inducers such as doxorubicin and the pan-Akt inhibitor GSK690693, thus
   becoming valuable lead candidates for further optimization. Our results
   emphasize the possible role of 14-3-3 PPI inhibitors in anticancer
   combination therapies.
T2  - Chemmedchem
T1  - Discovery of 14-3-3 Protein- Protein Interaction Inhibitors that
 Sensitize Multidrug- Resistant Cancer Cells to Doxorubicin and the Akt
 Inhibitor GSK690693
IS  - 5, SI
VL  - 9
DO  - 10.1002/cmdc.201400044
SP  - 973
EP  - 983
ER  - 

@article{
author = "Mori, Mattia and Vignaroli, Giulia and Cau, Ylenia and Dinić, Jelena and Hill, Richard and Rossi, Matteo and Colecchia, David and Pešić, Milica and Link, Wolfgang and Chiariello, Mario and Ottmann, Christian and Botta, Maurizio",
year = "2014",
abstract = "14-3-3 is a family of highly conserved adapter proteins that is
   attracting much interest among medicinal chemists. Small-molecule
   inhibitors of 14-3-3 protein-protein interactions (PPIs) are in high
   demand, both as tools to increase our understanding of 14-3-3 actions in
   human diseases and as leads to develop innovative therapeutic agents.
   Herein we present the discovery of novel 14-3-3 PPI inhibitors through a
   multidisciplinary strategy combining molecular modeling, organic
   synthesis, image-based high-content analysis of reporter cells, and in
   vitro assays using cancer cells. Notably, the two most active compounds
   promoted the translocation of c-Abl and FOXO pro-apoptotic factors into
   the nucleus and sensitized multidrug-resistant cancer cells to apoptotic
   inducers such as doxorubicin and the pan-Akt inhibitor GSK690693, thus
   becoming valuable lead candidates for further optimization. Our results
   emphasize the possible role of 14-3-3 PPI inhibitors in anticancer
   combination therapies.",
journal = "Chemmedchem",
title = "Discovery of 14-3-3 Protein- Protein Interaction Inhibitors that
 Sensitize Multidrug- Resistant Cancer Cells to Doxorubicin and the Akt
 Inhibitor GSK690693",
number = "5, SI",
volume = "9",
doi = "10.1002/cmdc.201400044",
pages = "973-983"
}

Mori, M., Vignaroli, G., Cau, Y., Dinić, J., Hill, R., Rossi, M., Colecchia, D., Pešić, M., Link, W., Chiariello, M., Ottmann, C.,& Botta, M.. (2014). Discovery of 14-3-3 Protein- Protein Interaction Inhibitors that
 Sensitize Multidrug- Resistant Cancer Cells to Doxorubicin and the Akt
 Inhibitor GSK690693. in Chemmedchem, 9(5, SI), 973-983.
https://doi.org/10.1002/cmdc.201400044

Mori M, Vignaroli G, Cau Y, Dinić J, Hill R, Rossi M, Colecchia D, Pešić M, Link W, Chiariello M, Ottmann C, Botta M. Discovery of 14-3-3 Protein- Protein Interaction Inhibitors that
 Sensitize Multidrug- Resistant Cancer Cells to Doxorubicin and the Akt
 Inhibitor GSK690693. in Chemmedchem. 2014;9(5, SI):973-983.
doi:10.1002/cmdc.201400044 .

Mori, Mattia, Vignaroli, Giulia, Cau, Ylenia, Dinić, Jelena, Hill, Richard, Rossi, Matteo, Colecchia, David, Pešić, Milica, Link, Wolfgang, Chiariello, Mario, Ottmann, Christian, Botta, Maurizio, "Discovery of 14-3-3 Protein- Protein Interaction Inhibitors that
 Sensitize Multidrug- Resistant Cancer Cells to Doxorubicin and the Akt
 Inhibitor GSK690693" in Chemmedchem, 9, no. 5, SI (2014):973-983,
https://doi.org/10.1002/cmdc.201400044 . .