TY  - JOUR
AU  - Paunović, V.
AU  - Kosić, M.
AU  - Đorđević, S.
AU  - Žugić, A.
AU  - Đalinac, N.
AU  - Gašić, U.
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2016
UR  - http://www.ncbi.nlm.nih.gov/pubmed/27755961
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2563
AB  - Marrubium vulgare is a European medicinal plant with numerous beneficial effects on human health. The aim of the study was to isolate the plant ethanolic extract (MVE) and to investigate its anti-melanoma and anti-glioma effects. MVE was prepared by the modified pharmacopoeial percolation method and characterized by UHPLC-LTQ OrbiTrap MS. MVE dose-dependently reduced viability of melanoma (B16) and glioma (U251) cells, but not peripheral blood mononuclear cells. It arrested cell cycle in S+G2/M phase, which was associated with the activation of MAP kinase p38 and up-regulation of antiproliferative genes p53, p21 and p27. MVE induced oxidative stress, while antioxidants abrogated its antitumor effect. Furthermore, MVE induced mitochondrial depolarization, activation of caspase-9 and -3, Parp cleavage, phosphatidylserine exposure and DNA fragmentation. The mitochondrial apoptotic pathway was associated with the up-regulation of proapoptotic genes Pten, Bak1, Apaf1, and Puma and down-regulation of antiapoptotic genes survivin and Xiap. MVE also stimulated the expression of autophagy-related genes Atg5, Atg7, Atg12, Beclin-1, Gabarab and Sqstm1, as well as LC3-I conversion to the autophagosome associated LC3-II, while autophagy inhibitors exacerbated its cytotoxicity. Finally, the most abundant phenolic components of MVE, ferulic, p-hydroxybenzoic, caffeic and chlorogenic acids, did not exert a profound effect on viability of tumor cells, suggesting that other components individually or in concert are the mediators of the extracts' cytotoxicity. By demonstrating the ability of MVE to inhibit proliferation, induce apoptosis and cytoprotective autophagy, our results suggest that MVE, alone or combined with autophagy inhibitors, could be a good candidate for anti-melanoma and anti-glioma therapy.
T2  - Cellular and molecular biology (Noisy-le-Grand, France)
T1  - Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro.
IS  - 11
VL  - 62
DO  - 10.14715/cmb/2016.62.11.18
SP  - 108
EP  - 114
ER  - 

@article{
author = "Paunović, V. and Kosić, M. and Đorđević, S. and Žugić, A. and Đalinac, N. and Gašić, U. and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2016",
abstract = "Marrubium vulgare is a European medicinal plant with numerous beneficial effects on human health. The aim of the study was to isolate the plant ethanolic extract (MVE) and to investigate its anti-melanoma and anti-glioma effects. MVE was prepared by the modified pharmacopoeial percolation method and characterized by UHPLC-LTQ OrbiTrap MS. MVE dose-dependently reduced viability of melanoma (B16) and glioma (U251) cells, but not peripheral blood mononuclear cells. It arrested cell cycle in S+G2/M phase, which was associated with the activation of MAP kinase p38 and up-regulation of antiproliferative genes p53, p21 and p27. MVE induced oxidative stress, while antioxidants abrogated its antitumor effect. Furthermore, MVE induced mitochondrial depolarization, activation of caspase-9 and -3, Parp cleavage, phosphatidylserine exposure and DNA fragmentation. The mitochondrial apoptotic pathway was associated with the up-regulation of proapoptotic genes Pten, Bak1, Apaf1, and Puma and down-regulation of antiapoptotic genes survivin and Xiap. MVE also stimulated the expression of autophagy-related genes Atg5, Atg7, Atg12, Beclin-1, Gabarab and Sqstm1, as well as LC3-I conversion to the autophagosome associated LC3-II, while autophagy inhibitors exacerbated its cytotoxicity. Finally, the most abundant phenolic components of MVE, ferulic, p-hydroxybenzoic, caffeic and chlorogenic acids, did not exert a profound effect on viability of tumor cells, suggesting that other components individually or in concert are the mediators of the extracts' cytotoxicity. By demonstrating the ability of MVE to inhibit proliferation, induce apoptosis and cytoprotective autophagy, our results suggest that MVE, alone or combined with autophagy inhibitors, could be a good candidate for anti-melanoma and anti-glioma therapy.",
journal = "Cellular and molecular biology (Noisy-le-Grand, France)",
title = "Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro.",
number = "11",
volume = "62",
doi = "10.14715/cmb/2016.62.11.18",
pages = "108-114"
}

Paunović, V., Kosić, M., Đorđević, S., Žugić, A., Đalinac, N., Gašić, U., Trajković, V.,& Harhaji-Trajković, L.. (2016). Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro.. in Cellular and molecular biology (Noisy-le-Grand, France), 62(11), 108-114.
https://doi.org/10.14715/cmb/2016.62.11.18

Paunović V, Kosić M, Đorđević S, Žugić A, Đalinac N, Gašić U, Trajković V, Harhaji-Trajković L. Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro.. in Cellular and molecular biology (Noisy-le-Grand, France). 2016;62(11):108-114.
doi:10.14715/cmb/2016.62.11.18 .

Paunović, V., Kosić, M., Đorđević, S., Žugić, A., Đalinac, N., Gašić, U., Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro." in Cellular and molecular biology (Noisy-le-Grand, France), 62, no. 11 (2016):108-114,
https://doi.org/10.14715/cmb/2016.62.11.18 . .

TY  - JOUR
AU  - Tovilović-Kovačević, Gordana
AU  - Ristić, Biljana
AU  - Milenković, Marina
AU  - Stanojević, Maja
AU  - Trajković, Vladimir
PY  - 2014
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6346
AB  - Macroautophagy (hereafter referred to as autophagy) is an evolutionary conserved catabolic process in which the cytoplasmic content is sequestered and degraded by the lysosomal machinery in order to maintain cellular homeostasis or provide energy during metabolic and hypoxic stress. It also represents an important component of the host response against infectious agents, performing surveillance and effector functions involved in detection and clearance of pathogens, including viruses. Moreover, it appears that autophagy plays a major role in determining the fate of both virally infected and uninfected cells by blocking or promoting their death in a virus- and cell-type-dependent manner. We here review the current knowledge on the complex involvement of autophagy in survival and death of the host cells during viral infection, focusing on the molecular mechanisms underlying viral modulation of autophagic response and its interference with the cell death pathways. We also discuss a possible significance of the autophagy-dependent modulation of cell death for the outcome and therapy of viral infections, emphasizing the need for a time- and cell-type-dependent fine-tuning of the autophagic response in achieving an optimal balance between beneficial and adverse effects.
PB  - John Wiley & Sons, Inc.
T2  - Medicinal Research Reviews
T1  - The Role and Therapeutic Potential of Autophagy Modulation in Controlling Virus-Induced Cell Death
IS  - 4
VL  - 34
DO  - 10.1002/med.21303
SP  - 744
EP  - 767
ER  - 

@article{
author = "Tovilović-Kovačević, Gordana and Ristić, Biljana and Milenković, Marina and Stanojević, Maja and Trajković, Vladimir",
year = "2014",
abstract = "Macroautophagy (hereafter referred to as autophagy) is an evolutionary conserved catabolic process in which the cytoplasmic content is sequestered and degraded by the lysosomal machinery in order to maintain cellular homeostasis or provide energy during metabolic and hypoxic stress. It also represents an important component of the host response against infectious agents, performing surveillance and effector functions involved in detection and clearance of pathogens, including viruses. Moreover, it appears that autophagy plays a major role in determining the fate of both virally infected and uninfected cells by blocking or promoting their death in a virus- and cell-type-dependent manner. We here review the current knowledge on the complex involvement of autophagy in survival and death of the host cells during viral infection, focusing on the molecular mechanisms underlying viral modulation of autophagic response and its interference with the cell death pathways. We also discuss a possible significance of the autophagy-dependent modulation of cell death for the outcome and therapy of viral infections, emphasizing the need for a time- and cell-type-dependent fine-tuning of the autophagic response in achieving an optimal balance between beneficial and adverse effects.",
publisher = "John Wiley & Sons, Inc.",
journal = "Medicinal Research Reviews",
title = "The Role and Therapeutic Potential of Autophagy Modulation in Controlling Virus-Induced Cell Death",
number = "4",
volume = "34",
doi = "10.1002/med.21303",
pages = "744-767"
}

Tovilović-Kovačević, G., Ristić, B., Milenković, M., Stanojević, M.,& Trajković, V.. (2014). The Role and Therapeutic Potential of Autophagy Modulation in Controlling Virus-Induced Cell Death. in Medicinal Research Reviews
John Wiley & Sons, Inc.., 34(4), 744-767.
https://doi.org/10.1002/med.21303

Tovilović-Kovačević G, Ristić B, Milenković M, Stanojević M, Trajković V. The Role and Therapeutic Potential of Autophagy Modulation in Controlling Virus-Induced Cell Death. in Medicinal Research Reviews. 2014;34(4):744-767.
doi:10.1002/med.21303 .

Tovilović-Kovačević, Gordana, Ristić, Biljana, Milenković, Marina, Stanojević, Maja, Trajković, Vladimir, "The Role and Therapeutic Potential of Autophagy Modulation in Controlling Virus-Induced Cell Death" in Medicinal Research Reviews, 34, no. 4 (2014):744-767,
https://doi.org/10.1002/med.21303 . .

TY  - JOUR
AU  - Pantic, Igor
AU  - Harhaji-Trajković, Ljubica
AU  - Pantović, Aleksandar
AU  - Milošević, Nebojša
AU  - Trajković, Vladimir
PY  - 2012
UR  - 2-s2.0-84860523993
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6225
AB  - The aim of our study was to employ fractal analysis for evaluation of ultrastructural changes during early stages of apoptosis. Apoptosis was induced in U251 human glioma cell line by exposure to UVB light. The cells were visualized by optical phase-contrast microscopy and photographed before the UV treatment, immediately after the treatment, as well as at 30 min intervals during 5h observation period. For each of the 32 cells analyzed, cellular and nuclear fractal dimension, as well as nuclear lacunarity, were determined at each time point. Our data demonstrate that cellular ultrastructural complexity determined by fractal dimension and lacunarity significantly decreases after the UV irradiation, with the nuclear lacunarity being a particularly sensitive parameter in detecting early apoptosis. Importantly, fractal analysis was able to detect cellular apoptotic changes earlier than conventional flow cytometric analysis of phosphatidylserine exposure, DNA fragmentation and cell membrane permeabilization. These results indicate that fractal analysis might be a powerful and affordable method for non-invasive early identification of apoptosis in cell cultures.
PB  - Academic Press
T2  - Journal of Theoretical Biology
T1  - Changes in fractal dimension and lacunarity as early markers of UV-induced apoptosis
VL  - 303
DO  - 10.1016/j.jtbi.2012.03.013
SP  - 87
EP  - 92
ER  - 

@article{
author = "Pantic, Igor and Harhaji-Trajković, Ljubica and Pantović, Aleksandar and Milošević, Nebojša and Trajković, Vladimir",
year = "2012",
abstract = "The aim of our study was to employ fractal analysis for evaluation of ultrastructural changes during early stages of apoptosis. Apoptosis was induced in U251 human glioma cell line by exposure to UVB light. The cells were visualized by optical phase-contrast microscopy and photographed before the UV treatment, immediately after the treatment, as well as at 30 min intervals during 5h observation period. For each of the 32 cells analyzed, cellular and nuclear fractal dimension, as well as nuclear lacunarity, were determined at each time point. Our data demonstrate that cellular ultrastructural complexity determined by fractal dimension and lacunarity significantly decreases after the UV irradiation, with the nuclear lacunarity being a particularly sensitive parameter in detecting early apoptosis. Importantly, fractal analysis was able to detect cellular apoptotic changes earlier than conventional flow cytometric analysis of phosphatidylserine exposure, DNA fragmentation and cell membrane permeabilization. These results indicate that fractal analysis might be a powerful and affordable method for non-invasive early identification of apoptosis in cell cultures.",
publisher = "Academic Press",
journal = "Journal of Theoretical Biology",
title = "Changes in fractal dimension and lacunarity as early markers of UV-induced apoptosis",
volume = "303",
doi = "10.1016/j.jtbi.2012.03.013",
pages = "87-92"
}

Pantic, I., Harhaji-Trajković, L., Pantović, A., Milošević, N.,& Trajković, V.. (2012). Changes in fractal dimension and lacunarity as early markers of UV-induced apoptosis. in Journal of Theoretical Biology
Academic Press., 303, 87-92.
https://doi.org/10.1016/j.jtbi.2012.03.013

Pantic I, Harhaji-Trajković L, Pantović A, Milošević N, Trajković V. Changes in fractal dimension and lacunarity as early markers of UV-induced apoptosis. in Journal of Theoretical Biology. 2012;303:87-92.
doi:10.1016/j.jtbi.2012.03.013 .

Pantic, Igor, Harhaji-Trajković, Ljubica, Pantović, Aleksandar, Milošević, Nebojša, Trajković, Vladimir, "Changes in fractal dimension and lacunarity as early markers of UV-induced apoptosis" in Journal of Theoretical Biology, 303 (2012):87-92,
https://doi.org/10.1016/j.jtbi.2012.03.013 . .