TY  - JOUR
AU  - Marković, Zoran M.
AU  - Ristić, Biljana Z.
AU  - Arsikin, Katarina M.
AU  - Klisić, Đorđe G.
AU  - Harhaji-Trajković, Ljubica
AU  - Todorović-Marković, Biljana M.
AU  - Kepić, Dejan P.
AU  - Kravić-Stevović, Tamara K.
AU  - Jovanović, Svetlana P.
AU  - Milenković, Marina M.
AU  - Milivojević, Dusan D.
AU  - Bumbaširević, Vladimir Z.
AU  - Dramićanin, Miroslav D.
AU  - Trajković, Vladimir S.
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3587
AB  - The excellent photoluminescent properties of graphene quantum dots (GQD) makes them suitable candidates for biomedical applications, but their cytotoxicity has not been extensively studied. Here we show that electrochemically produced GQD irradiated with blue light (470. nm, 1. W) generate reactive oxygen species, including singlet oxygen, and kill U251 human glioma cells by causing oxidative stress. The cell death induced by photoexcited GQD displayed morphological and/or biochemical characteristics of both apoptosis (phosphatidylserine externalization, caspase activation, DNA fragmentation) and autophagy (formation of autophagic vesicles, LC3-I/LC3-II conversion, degradation of autophagic target p62). Moreover, a genetic inactivation of autophagy-essential LC3B protein partly abrogated the photodynamic cytotoxicity of GQD. These data indicate potential usefulness of GQD in photodynamic therapy, but also raise concerns about their possible toxicity.
PB  - Elsevier BV
T2  - Biomaterials
T1  - Graphene quantum dots as autophagy-inducing photodynamic agents
IS  - 29
VL  - 33
DO  - 10.1016/j.biomaterials.2012.06.060
SP  - 7084
EP  - 7092
ER  - 

@article{
author = "Marković, Zoran M. and Ristić, Biljana Z. and Arsikin, Katarina M. and Klisić, Đorđe G. and Harhaji-Trajković, Ljubica and Todorović-Marković, Biljana M. and Kepić, Dejan P. and Kravić-Stevović, Tamara K. and Jovanović, Svetlana P. and Milenković, Marina M. and Milivojević, Dusan D. and Bumbaširević, Vladimir Z. and Dramićanin, Miroslav D. and Trajković, Vladimir S.",
year = "2012",
abstract = "The excellent photoluminescent properties of graphene quantum dots (GQD) makes them suitable candidates for biomedical applications, but their cytotoxicity has not been extensively studied. Here we show that electrochemically produced GQD irradiated with blue light (470. nm, 1. W) generate reactive oxygen species, including singlet oxygen, and kill U251 human glioma cells by causing oxidative stress. The cell death induced by photoexcited GQD displayed morphological and/or biochemical characteristics of both apoptosis (phosphatidylserine externalization, caspase activation, DNA fragmentation) and autophagy (formation of autophagic vesicles, LC3-I/LC3-II conversion, degradation of autophagic target p62). Moreover, a genetic inactivation of autophagy-essential LC3B protein partly abrogated the photodynamic cytotoxicity of GQD. These data indicate potential usefulness of GQD in photodynamic therapy, but also raise concerns about their possible toxicity.",
publisher = "Elsevier BV",
journal = "Biomaterials",
title = "Graphene quantum dots as autophagy-inducing photodynamic agents",
number = "29",
volume = "33",
doi = "10.1016/j.biomaterials.2012.06.060",
pages = "7084-7092"
}

Marković, Z. M., Ristić, B. Z., Arsikin, K. M., Klisić, Đ. G., Harhaji-Trajković, L., Todorović-Marković, B. M., Kepić, D. P., Kravić-Stevović, T. K., Jovanović, S. P., Milenković, M. M., Milivojević, D. D., Bumbaširević, V. Z., Dramićanin, M. D.,& Trajković, V. S.. (2012). Graphene quantum dots as autophagy-inducing photodynamic agents. in Biomaterials
Elsevier BV., 33(29), 7084-7092.
https://doi.org/10.1016/j.biomaterials.2012.06.060

Marković ZM, Ristić BZ, Arsikin KM, Klisić ĐG, Harhaji-Trajković L, Todorović-Marković BM, Kepić DP, Kravić-Stevović TK, Jovanović SP, Milenković MM, Milivojević DD, Bumbaširević VZ, Dramićanin MD, Trajković VS. Graphene quantum dots as autophagy-inducing photodynamic agents. in Biomaterials. 2012;33(29):7084-7092.
doi:10.1016/j.biomaterials.2012.06.060 .

Marković, Zoran M., Ristić, Biljana Z., Arsikin, Katarina M., Klisić, Đorđe G., Harhaji-Trajković, Ljubica, Todorović-Marković, Biljana M., Kepić, Dejan P., Kravić-Stevović, Tamara K., Jovanović, Svetlana P., Milenković, Marina M., Milivojević, Dusan D., Bumbaširević, Vladimir Z., Dramićanin, Miroslav D., Trajković, Vladimir S., "Graphene quantum dots as autophagy-inducing photodynamic agents" in Biomaterials, 33, no. 29 (2012):7084-7092,
https://doi.org/10.1016/j.biomaterials.2012.06.060 . .

TY  - JOUR
AU  - Misirkić Marjanović, Maja
AU  - Janjetović, Kristina
AU  - Vučićević, Ljubica
AU  - Tovilović-Kovačević, Gordana
AU  - Ristić, Biljana Z
AU  - Vilimanović, Uros
AU  - Harhaji-Trajković, Ljubica
AU  - Sumarac-Dumanović, Mirjana S
AU  - Micić, Dragan D
AU  - Bumbaširević, Vladimir Z
AU  - Trajković, Vladimir S
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1232
AB  - The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR). a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3 beta shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-depenclent autophagic response might sensitize glioma cells to statin-induced apoptotic death. (C) 2011 Elsevier Ltd. All rights reserved.
T2  - Pharmacological Research
T1  - Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin
IS  - 1
VL  - 65
EP  - 119
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1232
ER  - 

@article{
author = "Misirkić Marjanović, Maja and Janjetović, Kristina and Vučićević, Ljubica and Tovilović-Kovačević, Gordana and Ristić, Biljana Z and Vilimanović, Uros and Harhaji-Trajković, Ljubica and Sumarac-Dumanović, Mirjana S and Micić, Dragan D and Bumbaširević, Vladimir Z and Trajković, Vladimir S",
year = "2012",
abstract = "The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR). a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3 beta shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-depenclent autophagic response might sensitize glioma cells to statin-induced apoptotic death. (C) 2011 Elsevier Ltd. All rights reserved.",
journal = "Pharmacological Research",
title = "Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin",
number = "1",
volume = "65",
pages = "119",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1232"
}

Misirkić Marjanović, M., Janjetović, K., Vučićević, L., Tovilović-Kovačević, G., Ristić, B. Z., Vilimanović, U., Harhaji-Trajković, L., Sumarac-Dumanović, M. S., Micić, D. D., Bumbaširević, V. Z.,& Trajković, V. S.. (2012). Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin. in Pharmacological Research, 65(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1232

Misirkić Marjanović M, Janjetović K, Vučićević L, Tovilović-Kovačević G, Ristić BZ, Vilimanović U, Harhaji-Trajković L, Sumarac-Dumanović MS, Micić DD, Bumbaširević VZ, Trajković VS. Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin. in Pharmacological Research. 2012;65(1):null-119.
https://hdl.handle.net/21.15107/rcub_ibiss_1232 .

Misirkić Marjanović, Maja, Janjetović, Kristina, Vučićević, Ljubica, Tovilović-Kovačević, Gordana, Ristić, Biljana Z, Vilimanović, Uros, Harhaji-Trajković, Ljubica, Sumarac-Dumanović, Mirjana S, Micić, Dragan D, Bumbaširević, Vladimir Z, Trajković, Vladimir S, "Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin" in Pharmacological Research, 65, no. 1 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1232 .