TY  - JOUR
AU  - Pantović, Aleksandar
AU  - Bošnjak, Mihajlo
AU  - Arsikin, Katarina
AU  - Kosić, Milica
AU  - Mandić, Miloš
AU  - Ristić, Biljana
AU  - Tošić, Jelena
AU  - Grujičić, Danica
AU  - Isaković, Aleksandra
AU  - Micic, Nikola
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S1357272516303946
UR  - https://www.scopus.com/record/display.uri?eid=2-s2.0-85008690027&origin=SingleRecordEmailAlert&dgcid=scalert_sc_search_email&txGid=BCBFF82A73D51FA0ED62BC41FE5E5987.wsnAw8kcdt7IPYLO0V48gA%3A29
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2512
AB  - We investigated the role of the intracellular energy-sensing AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in the in vitro antiglioma effect of the cyclooxygenase (COX) inhibitor indomethacin. Indomethacin was more potent than COX inhibitors diclofenac, naproxen, and ketoprofen in reducing the viability of U251 human glioma cells. Antiglioma effect of the drug was associated with p21 increase and G2M cell cycle arrest, as well as with oxidative stress, mitochondrial depolarization, caspase activation, and the induction of apoptosis. Indomethacin increased the phosphorylation of AMPK and its targets Raptor and acetyl-CoA carboxylase (ACC), and reduced the phosphorylation of mTOR and mTOR complex 1 (mTORC1) substrates p70S6 kinase and PRAS40 (Ser183). AMPK knockdown by RNA interference, as well as the treatment with the mTORC1 activator leucine, prevented indomethacin-mediated mTORC1 inhibition and cytotoxic action, while AMPK activators metformin and AICAR mimicked the effects of the drug. AMPK activation by indomethacin correlated with intracellular ATP depletion and increase in AMP/ATP ratio, and was apparently independent of COX inhibition or the increase in intracellular calcium. Finally, the toxicity of indomethacin towards primary human glioma cells was associated with the activation of AMPK/Raptor/ACC and subsequent suppression of mTORC1/S6K. By demonstrating the involvement of AMPK/mTORC1 pathway in the antiglioma action of indomethacin, our results support its further exploration in glioma therapy.
T2  - The International Journal of Biochemistry & Cell Biology
T1  - In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway
VL  - 83
DO  - 10.1016/j.biocel.2016.12.007
SP  - 84
EP  - 96
ER  - 

@article{
author = "Pantović, Aleksandar and Bošnjak, Mihajlo and Arsikin, Katarina and Kosić, Milica and Mandić, Miloš and Ristić, Biljana and Tošić, Jelena and Grujičić, Danica and Isaković, Aleksandra and Micic, Nikola and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2017",
abstract = "We investigated the role of the intracellular energy-sensing AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in the in vitro antiglioma effect of the cyclooxygenase (COX) inhibitor indomethacin. Indomethacin was more potent than COX inhibitors diclofenac, naproxen, and ketoprofen in reducing the viability of U251 human glioma cells. Antiglioma effect of the drug was associated with p21 increase and G2M cell cycle arrest, as well as with oxidative stress, mitochondrial depolarization, caspase activation, and the induction of apoptosis. Indomethacin increased the phosphorylation of AMPK and its targets Raptor and acetyl-CoA carboxylase (ACC), and reduced the phosphorylation of mTOR and mTOR complex 1 (mTORC1) substrates p70S6 kinase and PRAS40 (Ser183). AMPK knockdown by RNA interference, as well as the treatment with the mTORC1 activator leucine, prevented indomethacin-mediated mTORC1 inhibition and cytotoxic action, while AMPK activators metformin and AICAR mimicked the effects of the drug. AMPK activation by indomethacin correlated with intracellular ATP depletion and increase in AMP/ATP ratio, and was apparently independent of COX inhibition or the increase in intracellular calcium. Finally, the toxicity of indomethacin towards primary human glioma cells was associated with the activation of AMPK/Raptor/ACC and subsequent suppression of mTORC1/S6K. By demonstrating the involvement of AMPK/mTORC1 pathway in the antiglioma action of indomethacin, our results support its further exploration in glioma therapy.",
journal = "The International Journal of Biochemistry & Cell Biology",
title = "In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway",
volume = "83",
doi = "10.1016/j.biocel.2016.12.007",
pages = "84-96"
}

Pantović, A., Bošnjak, M., Arsikin, K., Kosić, M., Mandić, M., Ristić, B., Tošić, J., Grujičić, D., Isaković, A., Micic, N., Trajković, V.,& Harhaji-Trajković, L.. (2017). In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway. in The International Journal of Biochemistry & Cell Biology, 83, 84-96.
https://doi.org/10.1016/j.biocel.2016.12.007

Pantović A, Bošnjak M, Arsikin K, Kosić M, Mandić M, Ristić B, Tošić J, Grujičić D, Isaković A, Micic N, Trajković V, Harhaji-Trajković L. In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway. in The International Journal of Biochemistry & Cell Biology. 2017;83:84-96.
doi:10.1016/j.biocel.2016.12.007 .

Pantović, Aleksandar, Bošnjak, Mihajlo, Arsikin, Katarina, Kosić, Milica, Mandić, Miloš, Ristić, Biljana, Tošić, Jelena, Grujičić, Danica, Isaković, Aleksandra, Micic, Nikola, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "In vitro antiglioma action of indomethacin is mediated via AMP-activated protein kinase/mTOR complex 1 signalling pathway" in The International Journal of Biochemistry & Cell Biology, 83 (2017):84-96,
https://doi.org/10.1016/j.biocel.2016.12.007 . .

TY  - JOUR
AU  - Simić, Vladica
AU  - Pavlović, Slađan
AU  - Milošević, Suzana
AU  - Tošić, Jelena
AU  - Kljujić, Lolita
PY  - 1999
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5901
AB  - The center of biodiversity protected aquatics ecosistems in ex-situ terms: ,,Aquari­ um Kragujevac". The area of Balcan is one of six centers of biodiversity in Europe. Significant part of this area belongs to the teritory of Federal Republic of Yugoslavia. Except for the preservation of signifi­ cant biological diversity in the protected natural area, there is a permanent necessity for the protection, reproduction or breeding of large number of hidrobionts from different habitats only und strictly contro­ led artificial conditions. Modem and specially projected aquariums. There are hardly any objects for ex-situ preservation of biodiversity aquatics ecosistems on the teritory of Federal Republic of Yugosla­ via, and therefore object will be of ecological and scientific significance.
PB  - Belgrade: Institute for Nature Conservation of Serbia
T2  - Protection of Nature
T1  - Centar za očuvanje biodiverziteta akvatičnih ekosistema u ex-situ uslovima: "Akvarijum Kragujevac"
T1  - The center of biodiversity protected aquatics ecosistems in ex-situ terms: "Aquarium Kragujevac"
IS  - 2
VL  - 51
SP  - 171
EP  - 181
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5901
ER  - 

@article{
author = "Simić, Vladica and Pavlović, Slađan and Milošević, Suzana and Tošić, Jelena and Kljujić, Lolita",
year = "1999",
abstract = "The center of biodiversity protected aquatics ecosistems in ex-situ terms: ,,Aquari­ um Kragujevac". The area of Balcan is one of six centers of biodiversity in Europe. Significant part of this area belongs to the teritory of Federal Republic of Yugoslavia. Except for the preservation of signifi­ cant biological diversity in the protected natural area, there is a permanent necessity for the protection, reproduction or breeding of large number of hidrobionts from different habitats only und strictly contro­ led artificial conditions. Modem and specially projected aquariums. There are hardly any objects for ex-situ preservation of biodiversity aquatics ecosistems on the teritory of Federal Republic of Yugosla­ via, and therefore object will be of ecological and scientific significance.",
publisher = "Belgrade: Institute for Nature Conservation of Serbia",
journal = "Protection of Nature",
title = "Centar za očuvanje biodiverziteta akvatičnih ekosistema u ex-situ uslovima: "Akvarijum Kragujevac", The center of biodiversity protected aquatics ecosistems in ex-situ terms: "Aquarium Kragujevac"",
number = "2",
volume = "51",
pages = "171-181",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5901"
}

Simić, V., Pavlović, S., Milošević, S., Tošić, J.,& Kljujić, L.. (1999). Centar za očuvanje biodiverziteta akvatičnih ekosistema u ex-situ uslovima: "Akvarijum Kragujevac". in Protection of Nature
Belgrade: Institute for Nature Conservation of Serbia., 51(2), 171-181.
https://hdl.handle.net/21.15107/rcub_ibiss_5901

Simić V, Pavlović S, Milošević S, Tošić J, Kljujić L. Centar za očuvanje biodiverziteta akvatičnih ekosistema u ex-situ uslovima: "Akvarijum Kragujevac". in Protection of Nature. 1999;51(2):171-181.
https://hdl.handle.net/21.15107/rcub_ibiss_5901 .

Simić, Vladica, Pavlović, Slađan, Milošević, Suzana, Tošić, Jelena, Kljujić, Lolita, "Centar za očuvanje biodiverziteta akvatičnih ekosistema u ex-situ uslovima: "Akvarijum Kragujevac"" in Protection of Nature, 51, no. 2 (1999):171-181,
https://hdl.handle.net/21.15107/rcub_ibiss_5901 .