TY  - JOUR
AU  - Paunović, Verica
AU  - Kosic, Milica
AU  - Đorđević, S.
AU  - Žugić, Ana
AU  - Đalinac, Nataša
AU  - Gašić, Uroš M.
AU  - Trajković, Vladimir S.
AU  - Harhaji-Trajkovic, Ljubica
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2434
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.
PB  - C M B  Assoc, Poitiers
T2  - Cellular and Molecular Biology
T1  - Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro
VL  - 62
IS  - 11
SP  - 108
EP  - 114
DO  - 10.14715/cmb/2016.62.11.18
ER  - 

@article{
author = "Paunović, Verica and Kosic, Milica and Đorđević, S. and Žugić, Ana and Đalinac, Nataša and Gašić, Uroš M. and Trajković, Vladimir S. and Harhaji-Trajkovic, 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.",
publisher = "C M B  Assoc, Poitiers",
journal = "Cellular and Molecular Biology",
title = "Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro",
volume = "62",
number = "11",
pages = "108-114",
doi = "10.14715/cmb/2016.62.11.18"
}

Paunović, V., Kosic, M., Đorđević, S., Žugić, A., Đalinac, N., Gašić, U. M., Trajković, V. S.,& Harhaji-Trajkovic, L.. (2016). Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro. in Cellular and Molecular Biology
C M B  Assoc, Poitiers., 62(11), 108-114.
https://doi.org/10.14715/cmb/2016.62.11.18

Paunović V, Kosic M, Đorđević S, Žugić A, Đalinac N, Gašić UM, Trajković VS, Harhaji-Trajkovic L. Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro. in Cellular and Molecular Biology. 2016;62(11):108-114.
doi:10.14715/cmb/2016.62.11.18 .

Paunović, Verica, Kosic, Milica, Đorđević, S., Žugić, Ana, Đalinac, Nataša, Gašić, Uroš M., Trajković, Vladimir S., Harhaji-Trajkovic, Ljubica, "Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro" in Cellular and Molecular Biology, 62, no. 11 (2016):108-114,
https://doi.org/10.14715/cmb/2016.62.11.18 . .

TY  - JOUR
AU  - Markovic, M
AU  - Knezevic, N
AU  - Momčilović, Miljana
AU  - Grgurić-Šipka, Sanja
AU  - Harhaji-Trajkovic, Ljubica
AU  - Trajković, Vladimir S.
AU  - Stojkovic, MM
AU  - Sabo, Tibor
AU  - Miljković, Đorđe
PY  - 2005
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/718
AB  - There has been a continuing effort for the discovery of novel platinum(IV)-based antitumor compounds with better therapeutic performances than cisplatin. In the present work, the anticancer action of recently synthesized Pt(IV)-based complex [Pt(HPxSC)Cl-3] was investigated using rat and human astrocytoma cell lines C6 and U251. [Pt(HPxSC)Cl-3] markedly reduced the number of cultured astrocytoma Cells (IC50, 80 mu M), as determined by crystal violet assay. The Pt(IV) complex induced apoptotic death of tumor cells, as flow cytometry analysis of the propidium iodide-stained cellular DNA revealed approx. 30% of hypodiploid cells in [Pt(HPxSC)Cl-3]-treated astrocytoma cell cultures. On the other hand, [Pt(HPxSC)Cl-3] at 200 mu M did not affect the viability of rat primary astrocytes, unlike the established anticancer drug cisplatin, which displayed high toxicity toward both astrocytoma cells (IC50, 15 mu M) and primary astrocytes (IC50, 20 mu M). Moreover, [Pt(HPxSC)Cl-3] at 100 mu M did not interfere with the ability of rat peritoneal macrophages to produce important antitumor molecules nitric oxide and tumor necrosis factor-a. Finally, we assessed the ability of [Pt(HPxSC)Cl-3] to restrain growth of some bacterial and yeast strains, but it showed rather limited antimicrobial activity. (c) 2005 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - European Journal of Pharmacology
T1  - [Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties
VL  - 517
IS  - 1-2
SP  - 28
EP  - 34
DO  - 10.1016/j.ejphar.2005.05.038
ER  - 

@article{
author = "Markovic, M and Knezevic, N and Momčilović, Miljana and Grgurić-Šipka, Sanja and Harhaji-Trajkovic, Ljubica and Trajković, Vladimir S. and Stojkovic, MM and Sabo, Tibor and Miljković, Đorđe",
year = "2005",
abstract = "There has been a continuing effort for the discovery of novel platinum(IV)-based antitumor compounds with better therapeutic performances than cisplatin. In the present work, the anticancer action of recently synthesized Pt(IV)-based complex [Pt(HPxSC)Cl-3] was investigated using rat and human astrocytoma cell lines C6 and U251. [Pt(HPxSC)Cl-3] markedly reduced the number of cultured astrocytoma Cells (IC50, 80 mu M), as determined by crystal violet assay. The Pt(IV) complex induced apoptotic death of tumor cells, as flow cytometry analysis of the propidium iodide-stained cellular DNA revealed approx. 30% of hypodiploid cells in [Pt(HPxSC)Cl-3]-treated astrocytoma cell cultures. On the other hand, [Pt(HPxSC)Cl-3] at 200 mu M did not affect the viability of rat primary astrocytes, unlike the established anticancer drug cisplatin, which displayed high toxicity toward both astrocytoma cells (IC50, 15 mu M) and primary astrocytes (IC50, 20 mu M). Moreover, [Pt(HPxSC)Cl-3] at 100 mu M did not interfere with the ability of rat peritoneal macrophages to produce important antitumor molecules nitric oxide and tumor necrosis factor-a. Finally, we assessed the ability of [Pt(HPxSC)Cl-3] to restrain growth of some bacterial and yeast strains, but it showed rather limited antimicrobial activity. (c) 2005 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "European Journal of Pharmacology",
title = "[Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties",
volume = "517",
number = "1-2",
pages = "28-34",
doi = "10.1016/j.ejphar.2005.05.038"
}

Markovic, M., Knezevic, N., Momčilović, M., Grgurić-Šipka, S., Harhaji-Trajkovic, L., Trajković, V. S., Stojkovic, M., Sabo, T.,& Miljković, Đ.. (2005). [Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties. in European Journal of Pharmacology
Elsevier Science Bv, Amsterdam., 517(1-2), 28-34.
https://doi.org/10.1016/j.ejphar.2005.05.038

Markovic M, Knezevic N, Momčilović M, Grgurić-Šipka S, Harhaji-Trajkovic L, Trajković VS, Stojkovic M, Sabo T, Miljković Đ. [Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties. in European Journal of Pharmacology. 2005;517(1-2):28-34.
doi:10.1016/j.ejphar.2005.05.038 .

Markovic, M, Knezevic, N, Momčilović, Miljana, Grgurić-Šipka, Sanja, Harhaji-Trajkovic, Ljubica, Trajković, Vladimir S., Stojkovic, MM, Sabo, Tibor, Miljković, Đorđe, "[Pt(HPxSC)Cl-3], a novel platinum(IV) compound with anticancer properties" in European Journal of Pharmacology, 517, no. 1-2 (2005):28-34,
https://doi.org/10.1016/j.ejphar.2005.05.038 . .