TY  - JOUR
AU  - Despotović, Ana
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6302
AB  - Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, characterized by a highly invasive nature and therapy resistance. Combination of menadione and ascorbic acid (AA+MD) exerts strong ROS-mediated anti-GBM activity in vitro. The objective of this study was to improve AA+MD anti-GBM potential by modulating the activity of Akt and c-Jun N-terminal kinase (JNK), molecules with an important role in GBM development. The effects of Akt and JNK modulation on AA+MD toxicity in U251 human glioblastoma cells were assessed by cell viability assays, flow cytometry, RNA interference and plasmid overexpression, and immunoblot analysis. The AA+MD induced severe oxidative stress, an early increase in Akt phosphorylation followed by its strong inhibition, persistent JNK activation, and U251 cell death. Small molecule Akt kinase inhibitor 10-DEBC enhanced, while pharmacological and genetic Akt activation decreased, AA+MD-induced toxicity. The U251 cell death potentiation by 10-DEBC correlated with an increase in the combination-induced autophagic flux and was abolished by genetic autophagy silencing. Additionally, pharmacological JNK inhibitor SP600125 augmented combination toxicity toward U251 cells, an effect linked with increased ROS accumulation. These results indicate that small Akt and JNK kinase inhibitors significantly enhance AA+MD anti-GBM effects by autophagy potentiation and amplifying deleterious ROS levels.
PB  - Basel: MDPI
T2  - Biomedicines
T1  - Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells
IS  - 10
VL  - 11
DO  - 10.3390/biomedicines11102652
SP  - 2652
ER  - 

@article{
author = "Despotović, Ana and Janjetović, Kristina and Zogović, Nevena and Tovilović-Kovačević, Gordana",
year = "2023",
abstract = "Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults, characterized by a highly invasive nature and therapy resistance. Combination of menadione and ascorbic acid (AA+MD) exerts strong ROS-mediated anti-GBM activity in vitro. The objective of this study was to improve AA+MD anti-GBM potential by modulating the activity of Akt and c-Jun N-terminal kinase (JNK), molecules with an important role in GBM development. The effects of Akt and JNK modulation on AA+MD toxicity in U251 human glioblastoma cells were assessed by cell viability assays, flow cytometry, RNA interference and plasmid overexpression, and immunoblot analysis. The AA+MD induced severe oxidative stress, an early increase in Akt phosphorylation followed by its strong inhibition, persistent JNK activation, and U251 cell death. Small molecule Akt kinase inhibitor 10-DEBC enhanced, while pharmacological and genetic Akt activation decreased, AA+MD-induced toxicity. The U251 cell death potentiation by 10-DEBC correlated with an increase in the combination-induced autophagic flux and was abolished by genetic autophagy silencing. Additionally, pharmacological JNK inhibitor SP600125 augmented combination toxicity toward U251 cells, an effect linked with increased ROS accumulation. These results indicate that small Akt and JNK kinase inhibitors significantly enhance AA+MD anti-GBM effects by autophagy potentiation and amplifying deleterious ROS levels.",
publisher = "Basel: MDPI",
journal = "Biomedicines",
title = "Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells",
number = "10",
volume = "11",
doi = "10.3390/biomedicines11102652",
pages = "2652"
}

Despotović, A., Janjetović, K., Zogović, N.,& Tovilović-Kovačević, G.. (2023). Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells. in Biomedicines
Basel: MDPI., 11(10), 2652.
https://doi.org/10.3390/biomedicines11102652

Despotović A, Janjetović K, Zogović N, Tovilović-Kovačević G. Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells. in Biomedicines. 2023;11(10):2652.
doi:10.3390/biomedicines11102652 .

Despotović, Ana, Janjetović, Kristina, Zogović, Nevena, Tovilović-Kovačević, Gordana, "Pharmacological Akt and JNK kinase inhibitors 10-DEBC and SP600125 potentiate anti-glioblastoma effect of menadione and ascorbic acid combination in human U251 glioblastoma cells" in Biomedicines, 11, no. 10 (2023):2652,
https://doi.org/10.3390/biomedicines11102652 . .

TY  - JOUR
AU  - Božinović, Nevena
AU  - Savva, Kyriaki
AU  - Rajić, Vladimir
AU  - Popović, Maja
AU  - Tošić, Dragana
AU  - Janjetović, Kristina
AU  - Despotović, Ana
AU  - Zogović, Nevena
AU  - Stratakis, Emmanuel
AU  - Petrović, Suzana
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6271
AB  - The creation of novel biocompatible Ti-based thin films with a Zr or Cu sub-layer modified by ultrafast laser processing is studied. To prepare bioactive surfaces, ultrafast laser processing is focused on the formation of laser-induced periodic surface structures (LIPSS) with the production of oxide phases at the surfaces. Two differently designed multilayer thin films Ti/Cu/Ti and Ti/Zr/Ti were deposited on the silicon using the ion sputtering method. The Ti thin film contains Cu or Zr sub-layer (thickness of 10 nm) at the 10 nm below the surface. The composition and surface morphology variations for these systems, deposited and laser-processed under the same experimental conditions, were caused only by different thermo-physical properties of the sub-layer (Cu or Zr). The surface morphology in the form of LIPSS, led to improved cell adhesion and stable cells/thin films interface compared to as-deposited samples. Field-emission scanning electron microscopy and MTT analysis revealed that laser processing of both systems increased cell adhesion, proliferation, and metabolical activity of L929 mouse fibroblast cells compared to non-modified flat surfaces. Overall, the biocompatibility of Zr-containing thin films is better than Ti/Cu/Ti system. Further, laser processing and formation of LIPSS makes Ti/Zr/Ti thin films excellent candidate for biomedical.
PB  - Amsterdam: Elsevier
T2  - Materials Chemistry and Physics
T1  - Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films
VL  - 308
DO  - 10.1016/j.matchemphys.2023.128286
SP  - 128286
ER  - 

@article{
author = "Božinović, Nevena and Savva, Kyriaki and Rajić, Vladimir and Popović, Maja and Tošić, Dragana and Janjetović, Kristina and Despotović, Ana and Zogović, Nevena and Stratakis, Emmanuel and Petrović, Suzana",
year = "2023",
abstract = "The creation of novel biocompatible Ti-based thin films with a Zr or Cu sub-layer modified by ultrafast laser processing is studied. To prepare bioactive surfaces, ultrafast laser processing is focused on the formation of laser-induced periodic surface structures (LIPSS) with the production of oxide phases at the surfaces. Two differently designed multilayer thin films Ti/Cu/Ti and Ti/Zr/Ti were deposited on the silicon using the ion sputtering method. The Ti thin film contains Cu or Zr sub-layer (thickness of 10 nm) at the 10 nm below the surface. The composition and surface morphology variations for these systems, deposited and laser-processed under the same experimental conditions, were caused only by different thermo-physical properties of the sub-layer (Cu or Zr). The surface morphology in the form of LIPSS, led to improved cell adhesion and stable cells/thin films interface compared to as-deposited samples. Field-emission scanning electron microscopy and MTT analysis revealed that laser processing of both systems increased cell adhesion, proliferation, and metabolical activity of L929 mouse fibroblast cells compared to non-modified flat surfaces. Overall, the biocompatibility of Zr-containing thin films is better than Ti/Cu/Ti system. Further, laser processing and formation of LIPSS makes Ti/Zr/Ti thin films excellent candidate for biomedical.",
publisher = "Amsterdam: Elsevier",
journal = "Materials Chemistry and Physics",
title = "Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films",
volume = "308",
doi = "10.1016/j.matchemphys.2023.128286",
pages = "128286"
}

Božinović, N., Savva, K., Rajić, V., Popović, M., Tošić, D., Janjetović, K., Despotović, A., Zogović, N., Stratakis, E.,& Petrović, S.. (2023). Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films. in Materials Chemistry and Physics
Amsterdam: Elsevier., 308, 128286.
https://doi.org/10.1016/j.matchemphys.2023.128286

Božinović N, Savva K, Rajić V, Popović M, Tošić D, Janjetović K, Despotović A, Zogović N, Stratakis E, Petrović S. Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films. in Materials Chemistry and Physics. 2023;308:128286.
doi:10.1016/j.matchemphys.2023.128286 .

Božinović, Nevena, Savva, Kyriaki, Rajić, Vladimir, Popović, Maja, Tošić, Dragana, Janjetović, Kristina, Despotović, Ana, Zogović, Nevena, Stratakis, Emmanuel, Petrović, Suzana, "Influence of zirconium and copper sub-layer in cell integrations on femtosecond laser-processed Ti thin films" in Materials Chemistry and Physics, 308 (2023):128286,
https://doi.org/10.1016/j.matchemphys.2023.128286 . .

TY  - JOUR
AU  - Despotović, Ana
AU  - Mirčić, Aleksandar
AU  - Misirlić-Denčić, Sonja
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
AU  - Zogović, Nevena
AU  - Tovilović-Kovačević, Gordana
PY  - 2022
UR  - https://www.hindawi.com/journals/omcl/2022/2998132/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5078
AB  - We investigated the ability of the ascorbic acid (AA) and menadione (MD) combination, the well-known reactive oxidative species- (ROS-) generating system, to induce autophagy in human U251 glioblastoma cells. A combination of AA and MD (AA+MD), in contrast to single treatments, induced necrosis-like cell death mediated by mitochondrial membrane depolarization and extremely high oxidative stress. AA+MD, and to a lesser extent MD alone, prompted the appearance of autophagy markers such as autophagic vacuoles, autophagosome-associated LC3-II protein, degradation of p62, and increased expression of beclin-1. While both MD and AA+MD increased phosphorylation of AMP-activated protein kinase (AMPK), the well-known autophagy promotor, only the combined treatment affected its downstream targets, mechanistic target of rapamycin complex 1 (mTORC1), Unc 51-like kinase 1 (ULK1), and increased the expression of several autophagy-related genes. Antioxidant N-acetyl cysteine reduced both MD- and AA+MD-induced autophagy, as well as changes in AMPK/mTORC1/ULK1 activity and cell death triggered by the drug combination. Pharmacological and genetic autophagy silencing abolished the toxicity of AA+MD, while autophagy upregulation enhanced the toxicity of both AA+MD and MD. Therefore, by upregulating oxidative stress, inhibiting mTORC1, and activating ULK1, AA converts MD-induced AMPK-dependent autophagy from nontoxic to cytotoxic. These results suggest that AA+MD or MD treatment in combination with autophagy inducers could be further investigated as a novel approach for glioblastoma therapy.
PB  - London: Hindawi Ltd.
T2  - Oxidative Medicine and Cellular Longevity
T1  - Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells
VL  - 2022
DO  - 10.1155/2022/2998132
SP  - 2998132
ER  - 

@article{
author = "Despotović, Ana and Mirčić, Aleksandar and Misirlić-Denčić, Sonja and Harhaji-Trajković, Ljubica and Trajković, Vladimir and Zogović, Nevena and Tovilović-Kovačević, Gordana",
year = "2022",
abstract = "We investigated the ability of the ascorbic acid (AA) and menadione (MD) combination, the well-known reactive oxidative species- (ROS-) generating system, to induce autophagy in human U251 glioblastoma cells. A combination of AA and MD (AA+MD), in contrast to single treatments, induced necrosis-like cell death mediated by mitochondrial membrane depolarization and extremely high oxidative stress. AA+MD, and to a lesser extent MD alone, prompted the appearance of autophagy markers such as autophagic vacuoles, autophagosome-associated LC3-II protein, degradation of p62, and increased expression of beclin-1. While both MD and AA+MD increased phosphorylation of AMP-activated protein kinase (AMPK), the well-known autophagy promotor, only the combined treatment affected its downstream targets, mechanistic target of rapamycin complex 1 (mTORC1), Unc 51-like kinase 1 (ULK1), and increased the expression of several autophagy-related genes. Antioxidant N-acetyl cysteine reduced both MD- and AA+MD-induced autophagy, as well as changes in AMPK/mTORC1/ULK1 activity and cell death triggered by the drug combination. Pharmacological and genetic autophagy silencing abolished the toxicity of AA+MD, while autophagy upregulation enhanced the toxicity of both AA+MD and MD. Therefore, by upregulating oxidative stress, inhibiting mTORC1, and activating ULK1, AA converts MD-induced AMPK-dependent autophagy from nontoxic to cytotoxic. These results suggest that AA+MD or MD treatment in combination with autophagy inducers could be further investigated as a novel approach for glioblastoma therapy.",
publisher = "London: Hindawi Ltd.",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells",
volume = "2022",
doi = "10.1155/2022/2998132",
pages = "2998132"
}

Despotović, A., Mirčić, A., Misirlić-Denčić, S., Harhaji-Trajković, L., Trajković, V., Zogović, N.,& Tovilović-Kovačević, G.. (2022). Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells. in Oxidative Medicine and Cellular Longevity
London: Hindawi Ltd.., 2022, 2998132.
https://doi.org/10.1155/2022/2998132

Despotović A, Mirčić A, Misirlić-Denčić S, Harhaji-Trajković L, Trajković V, Zogović N, Tovilović-Kovačević G. Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells. in Oxidative Medicine and Cellular Longevity. 2022;2022:2998132.
doi:10.1155/2022/2998132 .

Despotović, Ana, Mirčić, Aleksandar, Misirlić-Denčić, Sonja, Harhaji-Trajković, Ljubica, Trajković, Vladimir, Zogović, Nevena, Tovilović-Kovačević, Gordana, "Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells" in Oxidative Medicine and Cellular Longevity, 2022 (2022):2998132,
https://doi.org/10.1155/2022/2998132 . .

TY  - CONF
AU  - Dožić, Aleksandra
AU  - Ćetković, Dejan
AU  - Despotović, Ana
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Antonijević, Đorđe
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5739
AB  - The aim of this study was to investigate the properties of experimental calcium aluminate (CA) dental cement, synthesized from CaO×Al2O3 and CaCO3. Calcium silicate (Portland cement, PC) served as a control. The elastic modulus and maximum stress obtained using the universal testing machine showed that CA has greater mechanical resistance than the control PC. Scanning electron microscopy (SEM) analysis of cements specimens before and after soaking in phosphate buffer saline showed that hydrated cements exposed crystal particles of calcite and new aluminum containing phases on their surfaces, suggesting their bioactive potential. Biocompatibility of the CA dental cement was evaluated by observing L929 cells morphology using phase-contrast microscopy. Cells treated with CA extract preserved their structural integrity without any changes in cell morphology, but with a slightly inhibited proliferation rate after 24h treatment, while PC induced changes typical for cell death.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia
T1  - Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement
SP  - 327
EP  - 330
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5739
ER  - 

@conference{
author = "Dožić, Aleksandra and Ćetković, Dejan and Despotović, Ana and Janjetović, Kristina and Zogović, Nevena and Antonijević, Đorđe",
year = "2022",
abstract = "The aim of this study was to investigate the properties of experimental calcium aluminate (CA) dental cement, synthesized from CaO×Al2O3 and CaCO3. Calcium silicate (Portland cement, PC) served as a control. The elastic modulus and maximum stress obtained using the universal testing machine showed that CA has greater mechanical resistance than the control PC. Scanning electron microscopy (SEM) analysis of cements specimens before and after soaking in phosphate buffer saline showed that hydrated cements exposed crystal particles of calcite and new aluminum containing phases on their surfaces, suggesting their bioactive potential. Biocompatibility of the CA dental cement was evaluated by observing L929 cells morphology using phase-contrast microscopy. Cells treated with CA extract preserved their structural integrity without any changes in cell morphology, but with a slightly inhibited proliferation rate after 24h treatment, while PC induced changes typical for cell death.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia",
title = "Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement",
pages = "327-330",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5739"
}

Dožić, A., Ćetković, D., Despotović, A., Janjetović, K., Zogović, N.,& Antonijević, Đ.. (2022). Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement. in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 327-330.
https://hdl.handle.net/21.15107/rcub_ibiss_5739

Dožić A, Ćetković D, Despotović A, Janjetović K, Zogović N, Antonijević Đ. Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement. in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia. 2022;:327-330.
https://hdl.handle.net/21.15107/rcub_ibiss_5739 .

Dožić, Aleksandra, Ćetković, Dejan, Despotović, Ana, Janjetović, Kristina, Zogović, Nevena, Antonijević, Đorđe, "Surface morphology, compressive strength and biocompatibility of calcium aluminate dental cement" in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia (2022):327-330,
https://hdl.handle.net/21.15107/rcub_ibiss_5739 .

TY  - CONF
AU  - Janjetović, Kristina
AU  - Stamenković, Marina
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Despotović, Ana
AU  - Stevanović, Danijela
AU  - Mandić, Miloš
AU  - Kosić, Milica
AU  - Paunović, Verica
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Trajković, Vladimir
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5737
AB  - I pored stalnog napretka lečenja kancera, ova bolest ostaje druga po smrtnosti u svetu. Kako bi se skratio vremenski i finansijski zahtevan proces razvoja novih hemoterapeutika poslednjih desetak godina intezivno se radi na ispitivanju antikancerskog potencijala lekova koji se već koriste u terapiji drugih bolesti. U ovom radu smo proučavali potencijalni antikancerski efekat inhibitora protonske pumpe pantoprazola (PPZ), terapeutika koji se standardno koristi u lečenju kiselinskih gastrointestinalnih poremećaja. Citotoksični efekat PPZ je ispitivan u kulturama humanog U251 glioblastoma, humanog H460 nesitnoćelijskog karcinoma pluća i mišjeg B16 melanoma. Pokazano je da PPZ aktiviranoj apoptozi u svim ispitivanim ćelijskim linijama prethodi povećana produkcija reaktivnih vrsta kiseonika, depolarizacija mitohondrija i aktivacija kaspaza. U prisustvu PPZ detektovano je povećanje LC3 II proteina ukazujući na aktivaciju autofagije. Detaljnijim ispitivanjem mehanizma koji je u osnovi toksičnog efekta PPZ, utvrđeno je da PPZ aktivira AKT/AMPK signalni put u ispitivanim ćelijskim linijama i stimuliše AMPK zavisnu citoprotektivnu autofagiju u U251 i B16 ćelijskim linijama. Sa druge strane, autofagija aktivirana u ćelijama karcinoma pluća je citotoksična. Sumirano, PPZ ispoljava značajan antikancerski potencijal prema U251, H460 i B16 ćelijama izazivajući apoptozu, pri čemu uloga autofagije u smrti ćelija može biti citoprotektivna ili citotoksična i zavisi od tipa ćelija. Dodatna farmakološka modulacija autofagije mogla bi poboljšati antikancerski potencijal pantoprazola.
AB  - И поред сталног напретка лечења канцера, ова болест остаје друга по смртности у
свету. Како би се скратио временски и финансијски захтеван процес развоја нових
хемотерапеутика последњих десетак година интезивно се ради на испитивању
антиканцерског потенцијала лекова који се већ користе у терапији других болести.
У овом раду смо проучавали потенцијални антиканцерски ефекат инхибитора
протонске пумпе пантопразола (ППЗ), терапеутика који се стандардно користи у
лечењу киселинских гастроинтестиналних поремећаја. Цитотоксични ефекат ППЗ
је испитиван у културама хуманог U251 глиобластома, хуманог H460
неситноћелијског карцинома плућа и мишјег B16 меланома. Показано је да ППЗ
активираној апоптози у свим испитиваним ћелијским линијама претходи повећана
продукција реактивних врста кисеоника, деполаризација митохондрија и
активација каспаза. У присуству ППЗ детектовано је повећање LC3 II протеина
указујући на активацију аутофагије. Детаљнијим испитивањем механизма који је у
основи токсичног ефекта ППЗ, утврђено је да ППЗ активира AKT/AMPK сигнални
пут у испитиваним ћелијским линијама и стимулише AMPK зависну
цитопротективну аутофагију у U251 и B16 ћелијским линијама. Са друге стране,
аутофагија активирана у ћелијама карцинома плућа је цитотоксична. Сумирано,
ППЗ испољава значајан антиканцерски потенцијал према U251, H460 и B16
ћелијама изазивајући апоптозу, при чему улога аутофагије у смрти ћелија може
бити цитопротективна или цитотоксична и зависи од типа ћелија. Додатна
фармаколошка модулација аутофагије могла би побољшати антиканцерски
потенцијал пантопразола.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Antikancerski potencijal inhibitora protonske pumpe pantoprazola
T1  - Антиканцерски потенцијал инхибитора протонске пумпе пантопразола
SP  - 285
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5737
ER  - 

@conference{
author = "Janjetović, Kristina and Stamenković, Marina and Tovilović-Kovačević, Gordana and Zogović, Nevena and Despotović, Ana and Stevanović, Danijela and Mandić, Miloš and Kosić, Milica and Paunović, Verica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Trajković, Vladimir",
year = "2022",
abstract = "I pored stalnog napretka lečenja kancera, ova bolest ostaje druga po smrtnosti u svetu. Kako bi se skratio vremenski i finansijski zahtevan proces razvoja novih hemoterapeutika poslednjih desetak godina intezivno se radi na ispitivanju antikancerskog potencijala lekova koji se već koriste u terapiji drugih bolesti. U ovom radu smo proučavali potencijalni antikancerski efekat inhibitora protonske pumpe pantoprazola (PPZ), terapeutika koji se standardno koristi u lečenju kiselinskih gastrointestinalnih poremećaja. Citotoksični efekat PPZ je ispitivan u kulturama humanog U251 glioblastoma, humanog H460 nesitnoćelijskog karcinoma pluća i mišjeg B16 melanoma. Pokazano je da PPZ aktiviranoj apoptozi u svim ispitivanim ćelijskim linijama prethodi povećana produkcija reaktivnih vrsta kiseonika, depolarizacija mitohondrija i aktivacija kaspaza. U prisustvu PPZ detektovano je povećanje LC3 II proteina ukazujući na aktivaciju autofagije. Detaljnijim ispitivanjem mehanizma koji je u osnovi toksičnog efekta PPZ, utvrđeno je da PPZ aktivira AKT/AMPK signalni put u ispitivanim ćelijskim linijama i stimuliše AMPK zavisnu citoprotektivnu autofagiju u U251 i B16 ćelijskim linijama. Sa druge strane, autofagija aktivirana u ćelijama karcinoma pluća je citotoksična. Sumirano, PPZ ispoljava značajan antikancerski potencijal prema U251, H460 i B16 ćelijama izazivajući apoptozu, pri čemu uloga autofagije u smrti ćelija može biti citoprotektivna ili citotoksična i zavisi od tipa ćelija. Dodatna farmakološka modulacija autofagije mogla bi poboljšati antikancerski potencijal pantoprazola., И поред сталног напретка лечења канцера, ова болест остаје друга по смртности у
свету. Како би се скратио временски и финансијски захтеван процес развоја нових
хемотерапеутика последњих десетак година интезивно се ради на испитивању
антиканцерског потенцијала лекова који се већ користе у терапији других болести.
У овом раду смо проучавали потенцијални антиканцерски ефекат инхибитора
протонске пумпе пантопразола (ППЗ), терапеутика који се стандардно користи у
лечењу киселинских гастроинтестиналних поремећаја. Цитотоксични ефекат ППЗ
је испитиван у културама хуманог U251 глиобластома, хуманог H460
неситноћелијског карцинома плућа и мишјег B16 меланома. Показано је да ППЗ
активираној апоптози у свим испитиваним ћелијским линијама претходи повећана
продукција реактивних врста кисеоника, деполаризација митохондрија и
активација каспаза. У присуству ППЗ детектовано је повећање LC3 II протеина
указујући на активацију аутофагије. Детаљнијим испитивањем механизма који је у
основи токсичног ефекта ППЗ, утврђено је да ППЗ активира AKT/AMPK сигнални
пут у испитиваним ћелијским линијама и стимулише AMPK зависну
цитопротективну аутофагију у U251 и B16 ћелијским линијама. Са друге стране,
аутофагија активирана у ћелијама карцинома плућа је цитотоксична. Сумирано,
ППЗ испољава значајан антиканцерски потенцијал према U251, H460 и B16
ћелијама изазивајући апоптозу, при чему улога аутофагије у смрти ћелија може
бити цитопротективна или цитотоксична и зависи од типа ћелија. Додатна
фармаколошка модулација аутофагије могла би побољшати антиканцерски
потенцијал пантопразола.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Antikancerski potencijal inhibitora protonske pumpe pantoprazola, Антиканцерски потенцијал инхибитора протонске пумпе пантопразола",
pages = "285",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5737"
}

Janjetović, K., Stamenković, M., Tovilović-Kovačević, G., Zogović, N., Despotović, A., Stevanović, D., Mandić, M., Kosić, M., Paunović, V., Vučićević, L., Misirkić Marjanović, M.,& Trajković, V.. (2022). Antikancerski potencijal inhibitora protonske pumpe pantoprazola. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 285.
https://hdl.handle.net/21.15107/rcub_ibiss_5737

Janjetović K, Stamenković M, Tovilović-Kovačević G, Zogović N, Despotović A, Stevanović D, Mandić M, Kosić M, Paunović V, Vučićević L, Misirkić Marjanović M, Trajković V. Antikancerski potencijal inhibitora protonske pumpe pantoprazola. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:285.
https://hdl.handle.net/21.15107/rcub_ibiss_5737 .

Janjetović, Kristina, Stamenković, Marina, Tovilović-Kovačević, Gordana, Zogović, Nevena, Despotović, Ana, Stevanović, Danijela, Mandić, Miloš, Kosić, Milica, Paunović, Verica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Trajković, Vladimir, "Antikancerski potencijal inhibitora protonske pumpe pantoprazola" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):285,
https://hdl.handle.net/21.15107/rcub_ibiss_5737 .

TY  - CONF
AU  - Ćetković, Dejan
AU  - Dožić, Aleksandra
AU  - Despotović, Ana
AU  - Janjetović, Kristina
AU  - Zogović, Nevena
AU  - Antonijević, Đorđe
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5738
AB  - This study aimed to investigate the influence of ZrO2, Bi2O3 and SrF2 added as radiopacifying agents (30wt.%) into calcium silicate/hydroxyapatite-based dental cement on its physical and biological properties. Among investigated cements, the mixture containing Bi2O3 had the highest values of elastic modules and toughness, similarly to control – mineral trioxide aggregate (MTA). SEM analysis of all hydrated cements has shown that bioactive calcite and tobermorite phases were formed. Crystal violet assay showed that pure (undiluted) extracts of experimental cements did not affect cell viability, while MTA exhibited an extremely cytotoxic effect on L929 cells. In 1:4 dilutions all experimental mixtures significantly increased cell proliferation potential after 72h in comparison to untreated cells and MTA, which cytotoxic effect diminished with dilutions. Further studies are needed to determine which radiopacifyer has the most desirable properties for adequate dental cement fabrication.
PB  - Belgrade: Society of Physical Chemists of Serbia
C3  - Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia
T1  - Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite
SP  - 323
EP  - 326
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5738
ER  - 

@conference{
author = "Ćetković, Dejan and Dožić, Aleksandra and Despotović, Ana and Janjetović, Kristina and Zogović, Nevena and Antonijević, Đorđe",
year = "2022",
abstract = "This study aimed to investigate the influence of ZrO2, Bi2O3 and SrF2 added as radiopacifying agents (30wt.%) into calcium silicate/hydroxyapatite-based dental cement on its physical and biological properties. Among investigated cements, the mixture containing Bi2O3 had the highest values of elastic modules and toughness, similarly to control – mineral trioxide aggregate (MTA). SEM analysis of all hydrated cements has shown that bioactive calcite and tobermorite phases were formed. Crystal violet assay showed that pure (undiluted) extracts of experimental cements did not affect cell viability, while MTA exhibited an extremely cytotoxic effect on L929 cells. In 1:4 dilutions all experimental mixtures significantly increased cell proliferation potential after 72h in comparison to untreated cells and MTA, which cytotoxic effect diminished with dilutions. Further studies are needed to determine which radiopacifyer has the most desirable properties for adequate dental cement fabrication.",
publisher = "Belgrade: Society of Physical Chemists of Serbia",
journal = "Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia",
title = "Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite",
pages = "323-326",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5738"
}

Ćetković, D., Dožić, A., Despotović, A., Janjetović, K., Zogović, N.,& Antonijević, Đ.. (2022). Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite. in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia
Belgrade: Society of Physical Chemists of Serbia., 323-326.
https://hdl.handle.net/21.15107/rcub_ibiss_5738

Ćetković D, Dožić A, Despotović A, Janjetović K, Zogović N, Antonijević Đ. Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite. in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia. 2022;:323-326.
https://hdl.handle.net/21.15107/rcub_ibiss_5738 .

Ćetković, Dejan, Dožić, Aleksandra, Despotović, Ana, Janjetović, Kristina, Zogović, Nevena, Antonijević, Đorđe, "Effect of various radiopacifiers on selected physical properties and cytotoxicity of calcium silicate based dental cement enriched with hydroxyapatite" in Proceedings: 16th International Conference on Fundamental and Applied Aspects of Physical Chemistry: Physical Chemistry 2022, Vol. 2; 2022 Sep 26-30; Belgrade, Serbia (2022):323-326,
https://hdl.handle.net/21.15107/rcub_ibiss_5738 .

TY  - CONF
AU  - Despotović, Ana
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
PY  - 2021
UR  - https://www.sfrre2021belgrade.rs/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4724
AB  - The aim of this study was to investigate the role of necroptosis inhibitor necrostatin-1
(Nec-1) in death of human glioblastoma U251 cells exposed to ascorbic acid (AA), menadione(MD),
and their combination, in vitro. Nec-1 augmented cytotoxicity of AA+MD, and slightly increased
death of MD-treated U251 cells, as assessed by crystal violet (CV) assay. In line with previous, flow
cytometric analysis of annexin/propidium iodide-stained cells showed that Nec-1 triggered cell
death in MD and significantly enhanced ability of AA+MD to increase number of necrotic cells,
substantiating necrosis as the mechanism of U251 cell death induced by combined treatments
– AA+MD, Nec-1+MD, and Nec-1+AA+MD. Further, Nec-1 elevated mitochondrial and cellular
reactive oxygen species (ROS) generated by both MD and AA+MD co-treatment, as assessed
by flow cytometry analysis of MitoSOX- and DHR-stained cells, respectively. N-acetyl cysteine
(NAC), a well-known antioxidant, opposed U251 cell death induced by AA+MD, Nec-1+MD, and
Nec-1+AA+MD, indicating crucial role of oxidative stress in Nec-1-potentiated cytotoxicity of
MD and AA+MD. Also, Nec-1 activated AMP-activated protein kinase (AMPK), and its effector
molecule ULK1 (Ser317) over the level induced by MD and AA+MD, as showed by immunoblot.
AMPK, highly conserved serine/threonine protein kinase, is activated under the conditions of
oxidative stress probably as a consequence of depleted cellular ATP and elevated AMP levels.
This result implies important role of AMPK in necrosis detected in AA+MD-, Nec-1+MD-, and
Nec-1+AA+MD-treated U251 cells. Therefore, it can be concluded that ability of Nec-1 to enhance
cytotoxic potential of AA+MD co-treatment and trigger cytotoxicity of MD is associated with its
capacity to amplify cellular and mitochondrial ROS production, leading to necrosis-like cell
death of U251 cells. Obtained results reveal potential use of Nec-1 as anti-glioblastoma agent,
especially in combination with AA+MD.
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line
DO  - 10.1016/j.freeradbiomed.2021.08.081
SP  - 78
ER  - 

@conference{
author = "Despotović, Ana and Harhaji-Trajković, Ljubica and Trajković, Vladimir and Tovilović-Kovačević, Gordana and Zogović, Nevena",
year = "2021",
abstract = "The aim of this study was to investigate the role of necroptosis inhibitor necrostatin-1
(Nec-1) in death of human glioblastoma U251 cells exposed to ascorbic acid (AA), menadione(MD),
and their combination, in vitro. Nec-1 augmented cytotoxicity of AA+MD, and slightly increased
death of MD-treated U251 cells, as assessed by crystal violet (CV) assay. In line with previous, flow
cytometric analysis of annexin/propidium iodide-stained cells showed that Nec-1 triggered cell
death in MD and significantly enhanced ability of AA+MD to increase number of necrotic cells,
substantiating necrosis as the mechanism of U251 cell death induced by combined treatments
– AA+MD, Nec-1+MD, and Nec-1+AA+MD. Further, Nec-1 elevated mitochondrial and cellular
reactive oxygen species (ROS) generated by both MD and AA+MD co-treatment, as assessed
by flow cytometry analysis of MitoSOX- and DHR-stained cells, respectively. N-acetyl cysteine
(NAC), a well-known antioxidant, opposed U251 cell death induced by AA+MD, Nec-1+MD, and
Nec-1+AA+MD, indicating crucial role of oxidative stress in Nec-1-potentiated cytotoxicity of
MD and AA+MD. Also, Nec-1 activated AMP-activated protein kinase (AMPK), and its effector
molecule ULK1 (Ser317) over the level induced by MD and AA+MD, as showed by immunoblot.
AMPK, highly conserved serine/threonine protein kinase, is activated under the conditions of
oxidative stress probably as a consequence of depleted cellular ATP and elevated AMP levels.
This result implies important role of AMPK in necrosis detected in AA+MD-, Nec-1+MD-, and
Nec-1+AA+MD-treated U251 cells. Therefore, it can be concluded that ability of Nec-1 to enhance
cytotoxic potential of AA+MD co-treatment and trigger cytotoxicity of MD is associated with its
capacity to amplify cellular and mitochondrial ROS production, leading to necrosis-like cell
death of U251 cells. Obtained results reveal potential use of Nec-1 as anti-glioblastoma agent,
especially in combination with AA+MD.",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line",
doi = "10.1016/j.freeradbiomed.2021.08.081",
pages = "78"
}

Despotović, A., Harhaji-Trajković, L., Trajković, V., Tovilović-Kovačević, G.,& Zogović, N.. (2021). Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., 78.
https://doi.org/10.1016/j.freeradbiomed.2021.08.081

Despotović A, Harhaji-Trajković L, Trajković V, Tovilović-Kovačević G, Zogović N. Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:78.
doi:10.1016/j.freeradbiomed.2021.08.081 .

Despotović, Ana, Harhaji-Trajković, Ljubica, Trajković, Vladimir, Tovilović-Kovačević, Gordana, Zogović, Nevena, "Necrostatin-1 enhances menadione/ascorbic acid–induced oxidative stress and their cytotoxic potential in human glioblastoma U251 cell line" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):78,
https://doi.org/10.1016/j.freeradbiomed.2021.08.081 . .

TY  - CONF
AU  - Despotović, Ana
AU  - Zogović, Nevena
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
AU  - Tovilović-Kovačević, Gordana
PY  - 2021
UR  - https://www.sfrre2021belgrade.rs/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4723
AB  - Glioblastoma multiforme (GBM) represents the most common and aggressive brain tumor that still lacks effective treatment options. Tumorigenesis and progression of GBM is tightly connected with over-activation of PI3K/Akt pathway, as well as with perturbed reactive oxygen species (ROS) generation in tumor cells and microenvironment. Breaking the redox balance within the tumor cells by enhancing ROS production is one of the proposed strategies for the treatment of malignancies. The aim of this study was to investigate potential antiglioma effect of ascorbic acid (AA) and menadione (MD) combination (AA+MD), the well-known oxidative stress inducer, and determine the interplay between Akt kinase activity and ROS generation in AA+MD-treated human U251 glioblastoma cells. To this end, U251 cells were treated with AA, MD and AA+MD, in the presence or absence of antioxidant N-acetylcysteine (NAC) or selective Akt inhibitor 10-DEBC hydrochloride (DEBC). Cell viability was assessed using crystal violet and MTT assays, ROS production was evaluated by flow cytometry of dihydrorhodamine-labeled cells, while Akt activity was determined using immunoblot. In contrast to AA and MD alone, combined treatment significantly decreased viability of U251 cells. The prominent toxicity of AA+MD was accompanied by an increase in ROS generation and Akt inhibition. ROS scavenger NAC diminished both Akt inhibition and cytotoxic effect of AA+MD, suggesting that Akt inactivation and cell death induced by AA+MD are ROS-dependent. Additionally, specific Akt inhibitor DEBC further enhanced death of U251 cells and elevated AA+MD-induced ROS production. Collectively, these results suggest that PI3K/Akt serves as pro-survival pathway, and its abolishing due to excessive ROS accumulation leads to glioblastoma cell death. Further, a pro-survival role of PI3K/Akt might encompass ROS removal. In conclusion, treatment with AA and MD, particularly in combination with Akt-targeted therapy, has great potential in combating GBM which is worthy of further investigation.
PB  - Amsterdam : Elsevier
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt
DO  - 10.1016/j.freeradbiomed.2021.08.072
SP  - 69
ER  - 

@conference{
author = "Despotović, Ana and Zogović, Nevena and Trajković, Vladimir and Harhaji-Trajković, Ljubica and Tovilović-Kovačević, Gordana",
year = "2021",
abstract = "Glioblastoma multiforme (GBM) represents the most common and aggressive brain tumor that still lacks effective treatment options. Tumorigenesis and progression of GBM is tightly connected with over-activation of PI3K/Akt pathway, as well as with perturbed reactive oxygen species (ROS) generation in tumor cells and microenvironment. Breaking the redox balance within the tumor cells by enhancing ROS production is one of the proposed strategies for the treatment of malignancies. The aim of this study was to investigate potential antiglioma effect of ascorbic acid (AA) and menadione (MD) combination (AA+MD), the well-known oxidative stress inducer, and determine the interplay between Akt kinase activity and ROS generation in AA+MD-treated human U251 glioblastoma cells. To this end, U251 cells were treated with AA, MD and AA+MD, in the presence or absence of antioxidant N-acetylcysteine (NAC) or selective Akt inhibitor 10-DEBC hydrochloride (DEBC). Cell viability was assessed using crystal violet and MTT assays, ROS production was evaluated by flow cytometry of dihydrorhodamine-labeled cells, while Akt activity was determined using immunoblot. In contrast to AA and MD alone, combined treatment significantly decreased viability of U251 cells. The prominent toxicity of AA+MD was accompanied by an increase in ROS generation and Akt inhibition. ROS scavenger NAC diminished both Akt inhibition and cytotoxic effect of AA+MD, suggesting that Akt inactivation and cell death induced by AA+MD are ROS-dependent. Additionally, specific Akt inhibitor DEBC further enhanced death of U251 cells and elevated AA+MD-induced ROS production. Collectively, these results suggest that PI3K/Akt serves as pro-survival pathway, and its abolishing due to excessive ROS accumulation leads to glioblastoma cell death. Further, a pro-survival role of PI3K/Akt might encompass ROS removal. In conclusion, treatment with AA and MD, particularly in combination with Akt-targeted therapy, has great potential in combating GBM which is worthy of further investigation.",
publisher = "Amsterdam : Elsevier",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt",
doi = "10.1016/j.freeradbiomed.2021.08.072",
pages = "69"
}

Despotović, A., Zogović, N., Trajković, V., Harhaji-Trajković, L.,& Tovilović-Kovačević, G.. (2021). Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Amsterdam : Elsevier., 69.
https://doi.org/10.1016/j.freeradbiomed.2021.08.072

Despotović A, Zogović N, Trajković V, Harhaji-Trajković L, Tovilović-Kovačević G. Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt. in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:69.
doi:10.1016/j.freeradbiomed.2021.08.072 .

Despotović, Ana, Zogović, Nevena, Trajković, Vladimir, Harhaji-Trajković, Ljubica, Tovilović-Kovačević, Gordana, "Antiglioma effect of ascorbic acid and menadione combination in U251 glioblastoma  cell line is mediated by ROS-dependent downregulation of Akt" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):69,
https://doi.org/10.1016/j.freeradbiomed.2021.08.072 . .

TY  - JOUR
AU  - Despotović, Ana
AU  - Antonijević, Đorđe M
AU  - Ilić, Dragan
AU  - Zogović, Nevena
AU  - Jokanović, Vukoman R
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4430
AB  - Introduction Calcium silicate (CS) dental cements have numerous clinical indications in dentistry including pulp capping, root end surgery, perforation repair and apexification/apexogenesis treatment. Materials and methods Novel CS based dental cement with incorporation of SrCO3 radiopacifier named ALBO-DENT was used as an experimental cement material while Portland cement (Aalborg, Denmark) and ProRoot MTA (Tulsa Dental, USA) were used as controls. The radiopacity evaluation was performed using digital Trophy Radiographic system with an intention to precisely determine the minimum of radiopaque agent needed to confer to ISO radiopacity requirement. Thereafter, biocompatibility of material was tested in in vitro conditions in mouse fibrosarcoma L929 cell culture treated with materials’ extracts. Cell morphology was observed using phase-contrast microscopy, while cell viability was measured using crystal violet (CV) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assays. Results Radiopacity evaluation revealed that 30%wt addition of SrCO3 was necessary to achieve satisfactory radiopacity (3.45 mm Al). Cytotoxicity analysis using CV and MTT assays revealed that pure extracts of ALBO-DENT presented superior biocompatibility when compared to PC and MTA controls while serial dilutions of experimental cements’ extracts as well as that of PC and MTA did not influence L929 cell viability. Conclusions Novel formulation of CS cement – ALBO-DENT presented satisfactory radiopacity and adequate biocompatibility.
AB  - Uvod Kalcijum-silikatni (KS) dentalni cementi se koriste u brojnim kliničkim indikacijama u stomatologiji koje uključuju direktno prekrivanje pulpe, retrogradnu hirurgiju korena zuba, lečenje perforacija i apeksogenezu/apeksifikaciju. Materijali i metode U istraživanju je korišćen novosintetisani cement na bazi KS sa dodatkom SrCO3 kao kontrastnog agensa ALBO-DENTA, dok su kao kontrola korišćeni cement Portland (PC, Aalborg, Denmark) i ProRoot MTA (MTA, Tulsa Dental, USA). Rendgenokontrasnost je ispitivana digitalnom radiografijom primenom aparata Trophy, sa namerom da se precizno odredi minimum
kontrastnog agensa koji zadovoljava zahteve standarda ISO za rendgenkontrastnost. Biokompatibilnost materijala je ispitana in vitro, u kulturi ćelija mišjeg fibrosarkoma L929 tretiranoj ekstraktima ispitivanih materijala. Ćelijska morfologija je praćena upotrebom fazno-kontrastne mikroskopije, dok je vijabilnost ćelija utvrđivana kristal violet (KV) i 3-(4,5-dimetiltiazol-2-yl)-2,5-difenfl-tetrazolium bromid (MTT) esejima.
Rezultati Ispitivanje rendgenkontrastnosti je pokazalo da dodatak 30% SrCO3 dovodi do zadovoljavajućeg kontrasta materijala (3,45 mm Al). Analiza citotoksičnosti KV i MTT metodom je pokazala da čisti ekstrakt ALBO-DENTA pokazuje bolju biokompatibilnost u poređenju sa PC i MTA, dok serijska razblaženja ekstrakta ispitivanog cementa, kao i PC i MTA, nisu uticala na vijabilitet ćelija L929. Zaključci Novi cement na bazi KS – ALBO-DENT pokazao je zavodovoljavajuću rendgenkontrastnost i odgovarajuću biokompatibilnost.
PB  - Belgrade: Serbian Dental Journal
T2  - Serbian Dental Journal
T1  - Investigation of the radiopacity and cytotoxicity of ALBODENT – novel strontium carbonate incorporated calcium silicate based dental cement
T1  - Ispitivanje rendgenkontrastnosti i citotoksičnosti ALBO-DENTA – novog kalcijum-silikatnog cementa sa dodatkom stroncijumkarbonata
IS  - 2
VL  - 68
DO  - 10.2298/SGS2102068D
SP  - 68
EP  - 78
ER  - 

@article{
author = "Despotović, Ana and Antonijević, Đorđe M and Ilić, Dragan and Zogović, Nevena and Jokanović, Vukoman R",
year = "2021",
abstract = "Introduction Calcium silicate (CS) dental cements have numerous clinical indications in dentistry including pulp capping, root end surgery, perforation repair and apexification/apexogenesis treatment. Materials and methods Novel CS based dental cement with incorporation of SrCO3 radiopacifier named ALBO-DENT was used as an experimental cement material while Portland cement (Aalborg, Denmark) and ProRoot MTA (Tulsa Dental, USA) were used as controls. The radiopacity evaluation was performed using digital Trophy Radiographic system with an intention to precisely determine the minimum of radiopaque agent needed to confer to ISO radiopacity requirement. Thereafter, biocompatibility of material was tested in in vitro conditions in mouse fibrosarcoma L929 cell culture treated with materials’ extracts. Cell morphology was observed using phase-contrast microscopy, while cell viability was measured using crystal violet (CV) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assays. Results Radiopacity evaluation revealed that 30%wt addition of SrCO3 was necessary to achieve satisfactory radiopacity (3.45 mm Al). Cytotoxicity analysis using CV and MTT assays revealed that pure extracts of ALBO-DENT presented superior biocompatibility when compared to PC and MTA controls while serial dilutions of experimental cements’ extracts as well as that of PC and MTA did not influence L929 cell viability. Conclusions Novel formulation of CS cement – ALBO-DENT presented satisfactory radiopacity and adequate biocompatibility., Uvod Kalcijum-silikatni (KS) dentalni cementi se koriste u brojnim kliničkim indikacijama u stomatologiji koje uključuju direktno prekrivanje pulpe, retrogradnu hirurgiju korena zuba, lečenje perforacija i apeksogenezu/apeksifikaciju. Materijali i metode U istraživanju je korišćen novosintetisani cement na bazi KS sa dodatkom SrCO3 kao kontrastnog agensa ALBO-DENTA, dok su kao kontrola korišćeni cement Portland (PC, Aalborg, Denmark) i ProRoot MTA (MTA, Tulsa Dental, USA). Rendgenokontrasnost je ispitivana digitalnom radiografijom primenom aparata Trophy, sa namerom da se precizno odredi minimum
kontrastnog agensa koji zadovoljava zahteve standarda ISO za rendgenkontrastnost. Biokompatibilnost materijala je ispitana in vitro, u kulturi ćelija mišjeg fibrosarkoma L929 tretiranoj ekstraktima ispitivanih materijala. Ćelijska morfologija je praćena upotrebom fazno-kontrastne mikroskopije, dok je vijabilnost ćelija utvrđivana kristal violet (KV) i 3-(4,5-dimetiltiazol-2-yl)-2,5-difenfl-tetrazolium bromid (MTT) esejima.
Rezultati Ispitivanje rendgenkontrastnosti je pokazalo da dodatak 30% SrCO3 dovodi do zadovoljavajućeg kontrasta materijala (3,45 mm Al). Analiza citotoksičnosti KV i MTT metodom je pokazala da čisti ekstrakt ALBO-DENTA pokazuje bolju biokompatibilnost u poređenju sa PC i MTA, dok serijska razblaženja ekstrakta ispitivanog cementa, kao i PC i MTA, nisu uticala na vijabilitet ćelija L929. Zaključci Novi cement na bazi KS – ALBO-DENT pokazao je zavodovoljavajuću rendgenkontrastnost i odgovarajuću biokompatibilnost.",
publisher = "Belgrade: Serbian Dental Journal",
journal = "Serbian Dental Journal",
title = "Investigation of the radiopacity and cytotoxicity of ALBODENT – novel strontium carbonate incorporated calcium silicate based dental cement, Ispitivanje rendgenkontrastnosti i citotoksičnosti ALBO-DENTA – novog kalcijum-silikatnog cementa sa dodatkom stroncijumkarbonata",
number = "2",
volume = "68",
doi = "10.2298/SGS2102068D",
pages = "68-78"
}

Despotović, A., Antonijević, Đ. M., Ilić, D., Zogović, N.,& Jokanović, V. R.. (2021). Investigation of the radiopacity and cytotoxicity of ALBODENT – novel strontium carbonate incorporated calcium silicate based dental cement. in Serbian Dental Journal
Belgrade: Serbian Dental Journal., 68(2), 68-78.
https://doi.org/10.2298/SGS2102068D

Despotović A, Antonijević ĐM, Ilić D, Zogović N, Jokanović VR. Investigation of the radiopacity and cytotoxicity of ALBODENT – novel strontium carbonate incorporated calcium silicate based dental cement. in Serbian Dental Journal. 2021;68(2):68-78.
doi:10.2298/SGS2102068D .

Despotović, Ana, Antonijević, Đorđe M, Ilić, Dragan, Zogović, Nevena, Jokanović, Vukoman R, "Investigation of the radiopacity and cytotoxicity of ALBODENT – novel strontium carbonate incorporated calcium silicate based dental cement" in Serbian Dental Journal, 68, no. 2 (2021):68-78,
https://doi.org/10.2298/SGS2102068D . .

TY  - JOUR
AU  - Antonijević, Đorđe
AU  - Despotović, Ana
AU  - Biočanin, Vladimir
AU  - Milošević, Miloš
AU  - Trišić, Dijana
AU  - Lazović, Vladimir
AU  - Zogović, Nevena
AU  - Milašin, Jelena
AU  - Ilić, Dragan
PY  - 2021
UR  - https://www.sciencedirect.com/science/article/pii/S0272884221020794
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4464
AB  - The purpose of this study was to investigate the influence of different radiopacifiers on the physicochemical and biological properties of novel calcium silicate based endodontic ceramic enriched with bioactive nano-particulated hydroxyapatite – ECHA. Namely, ECHA was used as a basis for mixing with the following radiopacifiers: strontium fluoride (SrF2), zirconium dioxide (ZrO2) and bismuth oxide (Bi2O3). For comparison, Portland cement (PC) and mineral trioxide aggregate (MTA) were used. The following physicochemical characteristics were examined: the radiopacity, setting time, compressive strength, porosity, wettability and pH value. The biocompatibility of the cements was assessed by crystal violet, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and cell adhesion assays. The highest radiopacity was obtained for the ECHA + Bi2O3 mixture and MTA that were statistically significant in comparison to other materials (p < 0.05). Both initial and final setting times as well as compressive strengths were statistically lower for experimental cements than for PC and MTA (p < 0.05). The lowest total porosity was observed in the ECHA + ZrO2 group when compared with the other two experimental cements (p < 0.05), but not when compared with PC and MTA (p > 0.05). Experimental cements exhibited statistically higher contact angles of glycerol than PC and MTA (p < 0.05). For blood plasma, a statistical difference was found only between ECHA + Bi2O3 and PC (p < 0.05). All investigated materials had alkalization ability. Cell viability assays revealed that the extracts of tested cements did not exhibit cytotoxic effect on L929 cells. Scanning electron microscopy had shown a high degree of cell proliferation and adhesion of cells from apical papilla on experimental cements’ surfaces. Novel endodontic ceramics with nano-hydroxyapatite addition have satisfactory biological and physicochemical properties when compared to MTA and PC controls. Considerable lower setting time of experimental cements might present a huge advantage of these synthesized materials in clinical practice. SrF2 presents a novel promising radiopacifying agent for dental cements manufacturing.
PB  - Oxford : Elsevier
T2  - Ceramics International
T1  - Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic
IS  - 20
VL  - 47
DO  - 10.1016/j.ceramint.2021.07.052
SP  - 28913
EP  - 28923
ER  - 

@article{
author = "Antonijević, Đorđe and Despotović, Ana and Biočanin, Vladimir and Milošević, Miloš and Trišić, Dijana and Lazović, Vladimir and Zogović, Nevena and Milašin, Jelena and Ilić, Dragan",
year = "2021",
abstract = "The purpose of this study was to investigate the influence of different radiopacifiers on the physicochemical and biological properties of novel calcium silicate based endodontic ceramic enriched with bioactive nano-particulated hydroxyapatite – ECHA. Namely, ECHA was used as a basis for mixing with the following radiopacifiers: strontium fluoride (SrF2), zirconium dioxide (ZrO2) and bismuth oxide (Bi2O3). For comparison, Portland cement (PC) and mineral trioxide aggregate (MTA) were used. The following physicochemical characteristics were examined: the radiopacity, setting time, compressive strength, porosity, wettability and pH value. The biocompatibility of the cements was assessed by crystal violet, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and cell adhesion assays. The highest radiopacity was obtained for the ECHA + Bi2O3 mixture and MTA that were statistically significant in comparison to other materials (p < 0.05). Both initial and final setting times as well as compressive strengths were statistically lower for experimental cements than for PC and MTA (p < 0.05). The lowest total porosity was observed in the ECHA + ZrO2 group when compared with the other two experimental cements (p < 0.05), but not when compared with PC and MTA (p > 0.05). Experimental cements exhibited statistically higher contact angles of glycerol than PC and MTA (p < 0.05). For blood plasma, a statistical difference was found only between ECHA + Bi2O3 and PC (p < 0.05). All investigated materials had alkalization ability. Cell viability assays revealed that the extracts of tested cements did not exhibit cytotoxic effect on L929 cells. Scanning electron microscopy had shown a high degree of cell proliferation and adhesion of cells from apical papilla on experimental cements’ surfaces. Novel endodontic ceramics with nano-hydroxyapatite addition have satisfactory biological and physicochemical properties when compared to MTA and PC controls. Considerable lower setting time of experimental cements might present a huge advantage of these synthesized materials in clinical practice. SrF2 presents a novel promising radiopacifying agent for dental cements manufacturing.",
publisher = "Oxford : Elsevier",
journal = "Ceramics International",
title = "Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic",
number = "20",
volume = "47",
doi = "10.1016/j.ceramint.2021.07.052",
pages = "28913-28923"
}

Antonijević, Đ., Despotović, A., Biočanin, V., Milošević, M., Trišić, D., Lazović, V., Zogović, N., Milašin, J.,& Ilić, D.. (2021). Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic. in Ceramics International
Oxford : Elsevier., 47(20), 28913-28923.
https://doi.org/10.1016/j.ceramint.2021.07.052

Antonijević Đ, Despotović A, Biočanin V, Milošević M, Trišić D, Lazović V, Zogović N, Milašin J, Ilić D. Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic. in Ceramics International. 2021;47(20):28913-28923.
doi:10.1016/j.ceramint.2021.07.052 .

Antonijević, Đorđe, Despotović, Ana, Biočanin, Vladimir, Milošević, Miloš, Trišić, Dijana, Lazović, Vladimir, Zogović, Nevena, Milašin, Jelena, Ilić, Dragan, "Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic" in Ceramics International, 47, no. 20 (2021):28913-28923,
https://doi.org/10.1016/j.ceramint.2021.07.052 . .

TY  - JOUR
AU  - Antonijević, Đorđe
AU  - Despotović, Ana
AU  - Biočanin, Vladimir
AU  - Milošević, Miloš
AU  - Trišić, Dijana
AU  - Lazović, Vladimir
AU  - Zogović, Nevena
AU  - Milašin, Jelena
AU  - Ilić, Dragan
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0272884221020794
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4445
AB  - The purpose of this study was to investigate the influence of different radiopacifiers on the physicochemical and biological properties of novel calcium silicate based endodontic ceramic enriched with bioactive nano-particulated hydroxyapatite – ECHA. Namely, ECHA was used as a basis for mixing with the following radiopacifiers: strontium fluoride (SrF2), zirconium dioxide (ZrO2) and bismuth oxide (Bi2O3). For comparison, Portland cement (PC) and mineral trioxide aggregate (MTA) were used. The following physicochemical characteristics were examined: the radiopacity, setting time, compressive strength, porosity, wettability and pH value. The biocompatibility of the cements was assessed by crystal violet, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and cell adhesion assays. The highest radiopacity was obtained for the ECHA + Bi2O3 mixture and MTA that were statistically significant in comparison to other materials (p < 0.05). Both initial and final setting times as well as compressive strengths were statistically lower for experimental cements than for PC and MTA (p < 0.05). The lowest total porosity was observed in the ECHA + ZrO2 group when compared with the other two experimental cements (p < 0.05), but not when compared with PC and MTA (p > 0.05). Experimental cements exhibited statistically higher contact angles of glycerol than PC and MTA (p < 0.05). For blood plasma, a statistical difference was found only between ECHA + Bi2O3 and PC (p < 0.05). All investigated materials had alkalization ability. Cell viability assays revealed that the extracts of tested cements did not exhibit cytotoxic effect on L929 cells. Scanning electron microscopy had shown a high degree of cell proliferation and adhesion of cells from apical papilla on experimental cements’ surfaces. Novel endodontic ceramics with nano-hydroxyapatite addition have satisfactory biological and physicochemical properties when compared to MTA and PC controls. Considerable lower setting time of experimental cements might present a huge advantage of these synthesized materials in clinical practice. SrF2 presents a novel promising radiopacifying agent for dental cements manufacturing.
PB  - Oxford: Elsevier Ltd
T2  - Ceramics International
T1  - Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic
IS  - 20
VL  - 47
DO  - 10.1016/j.ceramint.2021.07.052
SP  - 28913
EP  - 28923
ER  - 

@article{
author = "Antonijević, Đorđe and Despotović, Ana and Biočanin, Vladimir and Milošević, Miloš and Trišić, Dijana and Lazović, Vladimir and Zogović, Nevena and Milašin, Jelena and Ilić, Dragan",
year = "2021",
abstract = "The purpose of this study was to investigate the influence of different radiopacifiers on the physicochemical and biological properties of novel calcium silicate based endodontic ceramic enriched with bioactive nano-particulated hydroxyapatite – ECHA. Namely, ECHA was used as a basis for mixing with the following radiopacifiers: strontium fluoride (SrF2), zirconium dioxide (ZrO2) and bismuth oxide (Bi2O3). For comparison, Portland cement (PC) and mineral trioxide aggregate (MTA) were used. The following physicochemical characteristics were examined: the radiopacity, setting time, compressive strength, porosity, wettability and pH value. The biocompatibility of the cements was assessed by crystal violet, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and cell adhesion assays. The highest radiopacity was obtained for the ECHA + Bi2O3 mixture and MTA that were statistically significant in comparison to other materials (p < 0.05). Both initial and final setting times as well as compressive strengths were statistically lower for experimental cements than for PC and MTA (p < 0.05). The lowest total porosity was observed in the ECHA + ZrO2 group when compared with the other two experimental cements (p < 0.05), but not when compared with PC and MTA (p > 0.05). Experimental cements exhibited statistically higher contact angles of glycerol than PC and MTA (p < 0.05). For blood plasma, a statistical difference was found only between ECHA + Bi2O3 and PC (p < 0.05). All investigated materials had alkalization ability. Cell viability assays revealed that the extracts of tested cements did not exhibit cytotoxic effect on L929 cells. Scanning electron microscopy had shown a high degree of cell proliferation and adhesion of cells from apical papilla on experimental cements’ surfaces. Novel endodontic ceramics with nano-hydroxyapatite addition have satisfactory biological and physicochemical properties when compared to MTA and PC controls. Considerable lower setting time of experimental cements might present a huge advantage of these synthesized materials in clinical practice. SrF2 presents a novel promising radiopacifying agent for dental cements manufacturing.",
publisher = "Oxford: Elsevier Ltd",
journal = "Ceramics International",
title = "Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic",
number = "20",
volume = "47",
doi = "10.1016/j.ceramint.2021.07.052",
pages = "28913-28923"
}

Antonijević, Đ., Despotović, A., Biočanin, V., Milošević, M., Trišić, D., Lazović, V., Zogović, N., Milašin, J.,& Ilić, D.. (2021). Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic. in Ceramics International
Oxford: Elsevier Ltd., 47(20), 28913-28923.
https://doi.org/10.1016/j.ceramint.2021.07.052

Antonijević Đ, Despotović A, Biočanin V, Milošević M, Trišić D, Lazović V, Zogović N, Milašin J, Ilić D. Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic. in Ceramics International. 2021;47(20):28913-28923.
doi:10.1016/j.ceramint.2021.07.052 .

Antonijević, Đorđe, Despotović, Ana, Biočanin, Vladimir, Milošević, Miloš, Trišić, Dijana, Lazović, Vladimir, Zogović, Nevena, Milašin, Jelena, Ilić, Dragan, "Influence of the addition of different radiopacifiers and bioactive nano-hydroxyapatite on physicochemical and biological properties of calcium silicate based endodontic ceramic" in Ceramics International, 47, no. 20 (2021):28913-28923,
https://doi.org/10.1016/j.ceramint.2021.07.052 . .

TY  - JOUR
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Despotović, Ana
AU  - Stamenković, Marina
AU  - Janjetović, Kristina
PY  - 2021
UR  - http://www.ajcr.us/files/ajcr0136757.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4679
AB  - Metformin has been known to treat type 2 diabetes for decades and is widely prescribed antidiabetic drug.
Recently, its anticancer potential has also been discovered. Moreover, metformin has low cost thus it has attained profound research interest. Comprehensing the complexity of the molecular regulatory networks in cancer provides a mode for advancement of research in cancer development and treatment. Metformin targets many pathways that play an important role in cancer cell survival outcome. Here, we described anticancer activity of metformin on the AMPK dependent/independent mechanisms regulating metabolism, oncogene/tumor suppressor signaling pathways together with the issue of clinical studies. We also provided brief overwiev about recently described metformin’s role in cancer immunity. Insight in these complex molecular networks, will simplify application of metformin in clinical trials and contribute to improvement of anti-cancer therapy.
PB  - Madison, USA : e-Century Publishing Corporation
T2  - American Journal of Cancer Research
T1  - Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context
IS  - 11
VL  - 11
SP  - 5625
EP  - 5643
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4679
ER  - 

@article{
author = "Misirkić Marjanović, Maja and Vučićević, Ljubica and Despotović, Ana and Stamenković, Marina and Janjetović, Kristina",
year = "2021",
abstract = "Metformin has been known to treat type 2 diabetes for decades and is widely prescribed antidiabetic drug.
Recently, its anticancer potential has also been discovered. Moreover, metformin has low cost thus it has attained profound research interest. Comprehensing the complexity of the molecular regulatory networks in cancer provides a mode for advancement of research in cancer development and treatment. Metformin targets many pathways that play an important role in cancer cell survival outcome. Here, we described anticancer activity of metformin on the AMPK dependent/independent mechanisms regulating metabolism, oncogene/tumor suppressor signaling pathways together with the issue of clinical studies. We also provided brief overwiev about recently described metformin’s role in cancer immunity. Insight in these complex molecular networks, will simplify application of metformin in clinical trials and contribute to improvement of anti-cancer therapy.",
publisher = "Madison, USA : e-Century Publishing Corporation",
journal = "American Journal of Cancer Research",
title = "Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context",
number = "11",
volume = "11",
pages = "5625-5643",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4679"
}

Misirkić Marjanović, M., Vučićević, L., Despotović, A., Stamenković, M.,& Janjetović, K.. (2021). Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context. in American Journal of Cancer Research
Madison, USA : e-Century Publishing Corporation., 11(11), 5625-5643.
https://hdl.handle.net/21.15107/rcub_ibiss_4679

Misirkić Marjanović M, Vučićević L, Despotović A, Stamenković M, Janjetović K. Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context. in American Journal of Cancer Research. 2021;11(11):5625-5643.
https://hdl.handle.net/21.15107/rcub_ibiss_4679 .

Misirkić Marjanović, Maja, Vučićević, Ljubica, Despotović, Ana, Stamenković, Marina, Janjetović, Kristina, "Dual anticancer role of metformin: an old drug regulating AMPK dependent/independent pathways in metabolic, oncogenic/tumorsuppresing and immunity context" in American Journal of Cancer Research, 11, no. 11 (2021):5625-5643,
https://hdl.handle.net/21.15107/rcub_ibiss_4679 .

TY  - CONF
AU  - Despotović, Ana
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6365
AB  - The goal of this study was to investigate ascorbate and menadione potential to induce oxidative stress and autophagy in U251 human glioblastoma cells in vitro. To this purpose, U251 cells were treated with single and combined doses of ascorbate and menadione. Cell viability was assessed by crystal violet test.
Changes in mitochondrial membrane potential, superoxide production, apoptosis, and autophagy were determined by flow cytometry using appropriate fluorochromes (JC-1, MitoSox, Annexin-Propidium iodide, and LysoTracker Red, respectively). Activation of the main autophagy repressor mTOR, and its target
S6K, expression of proautophagic protein p62, and conversion of LC3I to LC3II were assessed by immunoblot, while transfection with LC3 siRNA was used to determine the role of autophagy in glioma cell death. Treatment with single doses of ascorbate and menadione did not affect the viability of U251 cells, while their combination resulted in significant dose-dependent cytotoxic effect. This was associated with mitochondrial depolarization followed by increase in concentration of mitochondria-derived superoxide, and finally by apoptosis. Menadione and cotreatment induced increase in the content of acidic autophagic-like vesicles and autophagosome-associated LC3II protein, while decreased concentration of autophagic proteolysis substrate p62. The expression of LC3II was additionally elevated in the presence of proteolysis inhibitor, suggesting increase in autophagic flux. Reduced activity of mTOR and S6K indicate that detected autophagy was mTOR-dependent. Induced autophagy was cytotoxic, since its inhibition by LC3 RNA interference recovered viability of glioma cells. To conclude, combination of ascorbate and menadione synergistically induced oxidative stress, apoptosis, and mTOR-dependent cytotoxic autophagy in U251 cells.
PB  - Kragujevac: University of Kragujevac, Faculty of Medical Science
C3  - Final program and abstract book: 8th International Congress of Pathophysiology, Satelite Symposium: Oxidative Stress in Health and Disease: from Basic Science to Applied Investigations; 2018 Sep 03; Kragujevac, Serbia
T1  - Combination of menadione and ascorbate induces oxidative stress and mTOR-dependent cytotoxic autophagy
SP  - 34
EP  - 34
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6365
ER  - 

@conference{
author = "Despotović, Ana and Tovilović-Kovačević, Gordana and Zogović, Nevena and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2018",
abstract = "The goal of this study was to investigate ascorbate and menadione potential to induce oxidative stress and autophagy in U251 human glioblastoma cells in vitro. To this purpose, U251 cells were treated with single and combined doses of ascorbate and menadione. Cell viability was assessed by crystal violet test.
Changes in mitochondrial membrane potential, superoxide production, apoptosis, and autophagy were determined by flow cytometry using appropriate fluorochromes (JC-1, MitoSox, Annexin-Propidium iodide, and LysoTracker Red, respectively). Activation of the main autophagy repressor mTOR, and its target
S6K, expression of proautophagic protein p62, and conversion of LC3I to LC3II were assessed by immunoblot, while transfection with LC3 siRNA was used to determine the role of autophagy in glioma cell death. Treatment with single doses of ascorbate and menadione did not affect the viability of U251 cells, while their combination resulted in significant dose-dependent cytotoxic effect. This was associated with mitochondrial depolarization followed by increase in concentration of mitochondria-derived superoxide, and finally by apoptosis. Menadione and cotreatment induced increase in the content of acidic autophagic-like vesicles and autophagosome-associated LC3II protein, while decreased concentration of autophagic proteolysis substrate p62. The expression of LC3II was additionally elevated in the presence of proteolysis inhibitor, suggesting increase in autophagic flux. Reduced activity of mTOR and S6K indicate that detected autophagy was mTOR-dependent. Induced autophagy was cytotoxic, since its inhibition by LC3 RNA interference recovered viability of glioma cells. To conclude, combination of ascorbate and menadione synergistically induced oxidative stress, apoptosis, and mTOR-dependent cytotoxic autophagy in U251 cells.",
publisher = "Kragujevac: University of Kragujevac, Faculty of Medical Science",
journal = "Final program and abstract book: 8th International Congress of Pathophysiology, Satelite Symposium: Oxidative Stress in Health and Disease: from Basic Science to Applied Investigations; 2018 Sep 03; Kragujevac, Serbia",
title = "Combination of menadione and ascorbate induces oxidative stress and mTOR-dependent cytotoxic autophagy",
pages = "34-34",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6365"
}

Despotović, A., Tovilović-Kovačević, G., Zogović, N., Harhaji-Trajković, L.,& Trajković, V.. (2018). Combination of menadione and ascorbate induces oxidative stress and mTOR-dependent cytotoxic autophagy. in Final program and abstract book: 8th International Congress of Pathophysiology, Satelite Symposium: Oxidative Stress in Health and Disease: from Basic Science to Applied Investigations; 2018 Sep 03; Kragujevac, Serbia
Kragujevac: University of Kragujevac, Faculty of Medical Science., 34-34.
https://hdl.handle.net/21.15107/rcub_ibiss_6365

Despotović A, Tovilović-Kovačević G, Zogović N, Harhaji-Trajković L, Trajković V. Combination of menadione and ascorbate induces oxidative stress and mTOR-dependent cytotoxic autophagy. in Final program and abstract book: 8th International Congress of Pathophysiology, Satelite Symposium: Oxidative Stress in Health and Disease: from Basic Science to Applied Investigations; 2018 Sep 03; Kragujevac, Serbia. 2018;:34-34.
https://hdl.handle.net/21.15107/rcub_ibiss_6365 .

Despotović, Ana, Tovilović-Kovačević, Gordana, Zogović, Nevena, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Combination of menadione and ascorbate induces oxidative stress and mTOR-dependent cytotoxic autophagy" in Final program and abstract book: 8th International Congress of Pathophysiology, Satelite Symposium: Oxidative Stress in Health and Disease: from Basic Science to Applied Investigations; 2018 Sep 03; Kragujevac, Serbia (2018):34-34,
https://hdl.handle.net/21.15107/rcub_ibiss_6365 .