TY  - JOUR
AU  - Dinić, Jelena
AU  - Podolski-Renić, Ana
AU  - Jeremić, Marko
AU  - Pešić, Milica
PY  - 2018
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4049
AB  - Medicinal value of natural products comes from symbiotic and competitive evolution in Earth's complex biosphere. Billions of years of co-evolutionary interactions among millions of species have produced a large repertoire of defense molecules effective in fighting bacteria, viral, and fungal pathogens. Each species contains millions of different and useful molecules and new research technologies enabled the screening of molecules and complex mixtures from diverse biological sources. Traditional use of plants and other species led to the discovery of many bioactive compounds with various properties. In the last four decades, a large number of them were evaluated for their potential to treat cancer. Penetration of drugs into the cancer cell is necessary for their lethal pharmacological effect through interaction with intracellular target molecules. Increased activity of membrane efflux pumps reduces the intracellular drug accumulation, thereby preventing drug-target interactions. The discovery of the efflux transporter P-glycoprotein (P-gp) in multidrug resistant (MDR) cancer cells prompted the efforts in overcoming drug resistance by P-gp inhibition. The search for nontoxic anticancer agents from natural sources able to overcome MDR has been imperative in the field of drug design and discovery. Herein, we review various natural compounds from diverse sources emphasizing their potential to inhibit P-gp activity and/or expression.
PB  - Sharjah: Bentham Science Publishers
T2  - Current Pharmaceutical Design
T1  - Potential of Natural-Based Anticancer Compounds for P-Glycoprotein Inhibition
IS  - 36
VL  - 24
VL  - 4354
DO  - 10.2174/1381612825666190112164211
SP  - 4334
ER  - 

@article{
author = "Dinić, Jelena and Podolski-Renić, Ana and Jeremić, Marko and Pešić, Milica",
year = "2018",
abstract = "Medicinal value of natural products comes from symbiotic and competitive evolution in Earth's complex biosphere. Billions of years of co-evolutionary interactions among millions of species have produced a large repertoire of defense molecules effective in fighting bacteria, viral, and fungal pathogens. Each species contains millions of different and useful molecules and new research technologies enabled the screening of molecules and complex mixtures from diverse biological sources. Traditional use of plants and other species led to the discovery of many bioactive compounds with various properties. In the last four decades, a large number of them were evaluated for their potential to treat cancer. Penetration of drugs into the cancer cell is necessary for their lethal pharmacological effect through interaction with intracellular target molecules. Increased activity of membrane efflux pumps reduces the intracellular drug accumulation, thereby preventing drug-target interactions. The discovery of the efflux transporter P-glycoprotein (P-gp) in multidrug resistant (MDR) cancer cells prompted the efforts in overcoming drug resistance by P-gp inhibition. The search for nontoxic anticancer agents from natural sources able to overcome MDR has been imperative in the field of drug design and discovery. Herein, we review various natural compounds from diverse sources emphasizing their potential to inhibit P-gp activity and/or expression.",
publisher = "Sharjah: Bentham Science Publishers",
journal = "Current Pharmaceutical Design",
title = "Potential of Natural-Based Anticancer Compounds for P-Glycoprotein Inhibition",
number = "36",
volume = "24, 4354",
doi = "10.2174/1381612825666190112164211",
pages = "4334"
}

Dinić, J., Podolski-Renić, A., Jeremić, M.,& Pešić, M.. (2018). Potential of Natural-Based Anticancer Compounds for P-Glycoprotein Inhibition. in Current Pharmaceutical Design
Sharjah: Bentham Science Publishers., 24(36), 4334.
https://doi.org/10.2174/1381612825666190112164211

Dinić J, Podolski-Renić A, Jeremić M, Pešić M. Potential of Natural-Based Anticancer Compounds for P-Glycoprotein Inhibition. in Current Pharmaceutical Design. 2018;24(36):4334.
doi:10.2174/1381612825666190112164211 .

Dinić, Jelena, Podolski-Renić, Ana, Jeremić, Marko, Pešić, Milica, "Potential of Natural-Based Anticancer Compounds for P-Glycoprotein Inhibition" in Current Pharmaceutical Design, 24, no. 36 (2018):4334,
https://doi.org/10.2174/1381612825666190112164211 . .

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  - 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 . .