TY  - JOUR
AU  - Isaković, Anđelka M
AU  - Petričević, Sasa M.
AU  - Ristić, Slavica M.
AU  - Popadić, Dušan M.
AU  - Kravić-Stevović, Tamara K
AU  - Zogović, Nevena
AU  - Poljarević, Jelena M.
AU  - Živanović Radnić, Tatjana V
AU  - Sabo, Tibor J.
AU  - Isaković, Aleksandra J.
AU  - Marković, Ivanka D.
AU  - Trajković, Vladimir S.
AU  - Misirlić-Denčić, Sonja T
PY  - 2018
UR  - https://insights.ovid.com/crossref?an=00008390-201802000-00002
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3004
AB  - Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O,O-diethyl-(S,S)-ethylenediamine-N,N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound. Mouse melanoma B16 cell viability was assessed using acid phosphatase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, sulforhodamine B, and lactate dehydrogenase assays. Apoptosis and autophagy were investigated using flow cytometry, fluorescence and electron microscopy, and western blotting. In vivo antitumor potential was assessed in subcutaneous mouse melanoma model after 14 days of treatment with EE. Tumor mass and volume were measured, and RT-PCR was used for investigating the expression of autophagy-related, proapoptotic, and antiapoptotic molecules in tumor tissue. Investigated organic compound exerts significant cytotoxic effect against B16 cells. EE induced apoptosis, as confirmed by phosphatidyl serine externalisation, caspase activation, and ultrastructural features typical for apoptosis seen on fluorescence and electron microscopes. The apoptotic mechanism included prompt disruption of mitochondrial membrane potential and oxidative stress. No autophagy was observed. Antimelanoma action and apoptosis induction were confirmed in vivo, as EE decreased mass and volume of tumors, and increased expression of several proapoptotic genes. EE possesses significant antimelanoma action and causes caspase-dependent apoptosis mediated by mitochondrial damage and reactive oxygen species production. Decrease in tumor growth and increase in expression of proapoptotic genes in tumor tissue suggest that EE warrants further investigation as a candidate agent in treating melanoma.
PB  - Melanoma Research
T2  - Melanoma Research
T2  - Melanoma Research
T1  - In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid.
IS  - 1
VL  - 28
DO  - 10.1097/CMR.0000000000000409
SP  - 8
EP  - 20
ER  - 

@article{
author = "Isaković, Anđelka M and Petričević, Sasa M. and Ristić, Slavica M. and Popadić, Dušan M. and Kravić-Stevović, Tamara K and Zogović, Nevena and Poljarević, Jelena M. and Živanović Radnić, Tatjana V and Sabo, Tibor J. and Isaković, Aleksandra J. and Marković, Ivanka D. and Trajković, Vladimir S. and Misirlić-Denčić, Sonja T",
year = "2018",
abstract = "Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O,O-diethyl-(S,S)-ethylenediamine-N,N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound. Mouse melanoma B16 cell viability was assessed using acid phosphatase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, sulforhodamine B, and lactate dehydrogenase assays. Apoptosis and autophagy were investigated using flow cytometry, fluorescence and electron microscopy, and western blotting. In vivo antitumor potential was assessed in subcutaneous mouse melanoma model after 14 days of treatment with EE. Tumor mass and volume were measured, and RT-PCR was used for investigating the expression of autophagy-related, proapoptotic, and antiapoptotic molecules in tumor tissue. Investigated organic compound exerts significant cytotoxic effect against B16 cells. EE induced apoptosis, as confirmed by phosphatidyl serine externalisation, caspase activation, and ultrastructural features typical for apoptosis seen on fluorescence and electron microscopes. The apoptotic mechanism included prompt disruption of mitochondrial membrane potential and oxidative stress. No autophagy was observed. Antimelanoma action and apoptosis induction were confirmed in vivo, as EE decreased mass and volume of tumors, and increased expression of several proapoptotic genes. EE possesses significant antimelanoma action and causes caspase-dependent apoptosis mediated by mitochondrial damage and reactive oxygen species production. Decrease in tumor growth and increase in expression of proapoptotic genes in tumor tissue suggest that EE warrants further investigation as a candidate agent in treating melanoma.",
publisher = "Melanoma Research",
journal = "Melanoma Research, Melanoma Research",
title = "In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid.",
number = "1",
volume = "28",
doi = "10.1097/CMR.0000000000000409",
pages = "8-20"
}

Isaković, A. M., Petričević, S. M., Ristić, S. M., Popadić, D. M., Kravić-Stevović, T. K., Zogović, N., Poljarević, J. M., Živanović Radnić, T. V., Sabo, T. J., Isaković, A. J., Marković, I. D., Trajković, V. S.,& Misirlić-Denčić, S. T.. (2018). In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid.. in Melanoma Research
Melanoma Research., 28(1), 8-20.
https://doi.org/10.1097/CMR.0000000000000409

Isaković AM, Petričević SM, Ristić SM, Popadić DM, Kravić-Stevović TK, Zogović N, Poljarević JM, Živanović Radnić TV, Sabo TJ, Isaković AJ, Marković ID, Trajković VS, Misirlić-Denčić ST. In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid.. in Melanoma Research. 2018;28(1):8-20.
doi:10.1097/CMR.0000000000000409 .

Isaković, Anđelka M, Petričević, Sasa M., Ristić, Slavica M., Popadić, Dušan M., Kravić-Stevović, Tamara K, Zogović, Nevena, Poljarević, Jelena M., Živanović Radnić, Tatjana V, Sabo, Tibor J., Isaković, Aleksandra J., Marković, Ivanka D., Trajković, Vladimir S., Misirlić-Denčić, Sonja T, "In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid." in Melanoma Research, 28, no. 1 (2018):8-20,
https://doi.org/10.1097/CMR.0000000000000409 . .

TY  - JOUR
AU  - Mojić, Marija
AU  - Savic, Aleksandar
AU  - Arion, Vladimir B.
AU  - Bulatović, Mirna Z.
AU  - Poljarevic, Jelena M.
AU  - Miljković, Đorđe
AU  - Sabo, Tibor J.
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Grguric-Sipka, Sanja
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2310
AB  - Two p-cymene ruthenium chlorido complexes containing isobutyl (C1) and
   isoamyl (C2) esters of (S,S)ethylenediamine-N,N'-di-2-(3-cyclohexyl)
   propanoic acid as ligands were prepared from p-cymene ruthenium
   dichloride dimer and corresponding ester. All compounds have been
   characterized by elemental analysis, IR, ESI-MS, H-1 and C-13 NMR
   spectroscopy. Single crystal X-ray structure diffraction analysis of C1
   shows the usual piano-stool geometry of complexes, with coordination of
   ester ligand via nitrogen donor atoms. Ligands exhibit moderate
   anticancer activity (IC50 > 50 mu M), while the complexes were
   significantly more cytotoxic towards various cancer cell lines,
   including B16, A375, HCT116, A549 and MCF7 cells (IC50 min.-max. 2.9-8.0
   mu M). We stress that cisplatin resistant HCT116 cell line was highly
   sensitive to the treatment with C1 and C2 (IC50 values: 4.4 and 5.5 mu M
   versus IC50 > 120 mu M for cisplatin). In parallel, primary
   fibroblasts-MRC-5 were remarkably less affected by these compounds. (C)
   2013 Elsevier B. V. All rights reserved.
T2  - Journal of Organometallic Chemistry
T1  - Synthesis, X-ray structure and strong in vitro cytotoxicity of novel
 organoruthenium complexes
VL  - 749
DO  - 10.1016/j.jorganchem.2013.08.041
SP  - 142
EP  - 149
ER  - 

@article{
author = "Mojić, Marija and Savic, Aleksandar and Arion, Vladimir B. and Bulatović, Mirna Z. and Poljarevic, Jelena M. and Miljković, Đorđe and Sabo, Tibor J. and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Grguric-Sipka, Sanja",
year = "2014",
abstract = "Two p-cymene ruthenium chlorido complexes containing isobutyl (C1) and
   isoamyl (C2) esters of (S,S)ethylenediamine-N,N'-di-2-(3-cyclohexyl)
   propanoic acid as ligands were prepared from p-cymene ruthenium
   dichloride dimer and corresponding ester. All compounds have been
   characterized by elemental analysis, IR, ESI-MS, H-1 and C-13 NMR
   spectroscopy. Single crystal X-ray structure diffraction analysis of C1
   shows the usual piano-stool geometry of complexes, with coordination of
   ester ligand via nitrogen donor atoms. Ligands exhibit moderate
   anticancer activity (IC50 > 50 mu M), while the complexes were
   significantly more cytotoxic towards various cancer cell lines,
   including B16, A375, HCT116, A549 and MCF7 cells (IC50 min.-max. 2.9-8.0
   mu M). We stress that cisplatin resistant HCT116 cell line was highly
   sensitive to the treatment with C1 and C2 (IC50 values: 4.4 and 5.5 mu M
   versus IC50 > 120 mu M for cisplatin). In parallel, primary
   fibroblasts-MRC-5 were remarkably less affected by these compounds. (C)
   2013 Elsevier B. V. All rights reserved.",
journal = "Journal of Organometallic Chemistry",
title = "Synthesis, X-ray structure and strong in vitro cytotoxicity of novel
 organoruthenium complexes",
volume = "749",
doi = "10.1016/j.jorganchem.2013.08.041",
pages = "142-149"
}

Mojić, M., Savic, A., Arion, V. B., Bulatović, M. Z., Poljarevic, J. M., Miljković, Đ., Sabo, T. J., Mijatović, S., Maksimović-Ivanić, D.,& Grguric-Sipka, S.. (2014). Synthesis, X-ray structure and strong in vitro cytotoxicity of novel
 organoruthenium complexes. in Journal of Organometallic Chemistry, 749, 142-149.
https://doi.org/10.1016/j.jorganchem.2013.08.041

Mojić M, Savic A, Arion VB, Bulatović MZ, Poljarevic JM, Miljković Đ, Sabo TJ, Mijatović S, Maksimović-Ivanić D, Grguric-Sipka S. Synthesis, X-ray structure and strong in vitro cytotoxicity of novel
 organoruthenium complexes. in Journal of Organometallic Chemistry. 2014;749:142-149.
doi:10.1016/j.jorganchem.2013.08.041 .

Mojić, Marija, Savic, Aleksandar, Arion, Vladimir B., Bulatović, Mirna Z., Poljarevic, Jelena M., Miljković, Đorđe, Sabo, Tibor J., Mijatović, Sanja, Maksimović-Ivanić, Danijela, Grguric-Sipka, Sanja, "Synthesis, X-ray structure and strong in vitro cytotoxicity of novel
 organoruthenium complexes" in Journal of Organometallic Chemistry, 749 (2014):142-149,
https://doi.org/10.1016/j.jorganchem.2013.08.041 . .

TY  - JOUR
AU  - Kaluđerović, Goran
AU  - Miljković, Đorđe
AU  - Momčilović, Miljana
AU  - Đinović, Vesna
AU  - Mostarica Stojković, Marija
AU  - Sabo, Tibor
AU  - Trajković, Vladimir
PY  - 2005
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6014
AB  - The anticancer activity of platinum complexes has been known since the discovery of classical Pt(II)-based drug cisplatin. However, Pt(IV) complexes have greater inertness than corresponding Pt(II) complexes, thus allowing the oral administration and reducing the toxicity associated with platinum-based chemotherapy. Here, we describe the in vitro antitumor activity of some novel Pt(IV)-based agents against mouse fibrosarcoma L929 cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV) complexes with bidentate ethylenediamine-N,N'-di-3-propanoato esters was found to be markedly higher than that of their Pt(II) counterparts and comparable to the antitumor action of cisplatin. In contrast to cisplatin, which caused oxidative stress-independent apoptotic cell death of tumor cells, these Pt(IV) complexes induced oxygen radical-mediated tumor cell necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was markedly more rapid than that of cisplatin, indicating their potential usefulness in anticancer therapy.
PB  - John Wiley and Sons
T2  - International Journal of Cancer
T1  - Novel platinum(IV) complexes induce rapid tumor cell death in vitro
IS  - 3
VL  - 116
DO  - 10.1002/ijc.21080
SP  - 479
EP  - 486
ER  - 

@article{
author = "Kaluđerović, Goran and Miljković, Đorđe and Momčilović, Miljana and Đinović, Vesna and Mostarica Stojković, Marija and Sabo, Tibor and Trajković, Vladimir",
year = "2005",
abstract = "The anticancer activity of platinum complexes has been known since the discovery of classical Pt(II)-based drug cisplatin. However, Pt(IV) complexes have greater inertness than corresponding Pt(II) complexes, thus allowing the oral administration and reducing the toxicity associated with platinum-based chemotherapy. Here, we describe the in vitro antitumor activity of some novel Pt(IV)-based agents against mouse fibrosarcoma L929 cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV) complexes with bidentate ethylenediamine-N,N'-di-3-propanoato esters was found to be markedly higher than that of their Pt(II) counterparts and comparable to the antitumor action of cisplatin. In contrast to cisplatin, which caused oxidative stress-independent apoptotic cell death of tumor cells, these Pt(IV) complexes induced oxygen radical-mediated tumor cell necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was markedly more rapid than that of cisplatin, indicating their potential usefulness in anticancer therapy.",
publisher = "John Wiley and Sons",
journal = "International Journal of Cancer",
title = "Novel platinum(IV) complexes induce rapid tumor cell death in vitro",
number = "3",
volume = "116",
doi = "10.1002/ijc.21080",
pages = "479-486"
}

Kaluđerović, G., Miljković, Đ., Momčilović, M., Đinović, V., Mostarica Stojković, M., Sabo, T.,& Trajković, V.. (2005). Novel platinum(IV) complexes induce rapid tumor cell death in vitro. in International Journal of Cancer
John Wiley and Sons., 116(3), 479-486.
https://doi.org/10.1002/ijc.21080

Kaluđerović G, Miljković Đ, Momčilović M, Đinović V, Mostarica Stojković M, Sabo T, Trajković V. Novel platinum(IV) complexes induce rapid tumor cell death in vitro. in International Journal of Cancer. 2005;116(3):479-486.
doi:10.1002/ijc.21080 .

Kaluđerović, Goran, Miljković, Đorđe, Momčilović, Miljana, Đinović, Vesna, Mostarica Stojković, Marija, Sabo, Tibor, Trajković, Vladimir, "Novel platinum(IV) complexes induce rapid tumor cell death in vitro" in International Journal of Cancer, 116, no. 3 (2005):479-486,
https://doi.org/10.1002/ijc.21080 . .

TY  - JOUR
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Radović, Julijana
AU  - Miljković, Đorđe
AU  - Kaluđerović, Goran N.
AU  - Sabo, Tibor J
AU  - Trajković, Vladimir
PY  - 2005
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3839
AB  - The present study describes the ability of an anthraquinone derivative aloe emodin (AE) to reduce the cytotoxic activity of the platinum(II)-based anticancer agent cisplatin toward murine L929 fibrosarcoma and C6 glioma cell lines. The protective effect of AE was demonstrated by MTT and crystal violet assays for cell viability, and involved supression of cisplatin-induced apoptosis and necrosis, as assessed by lactate dehydrogenase release and flow cytometric analysis of DNA fragmentation or phosphatidylserine exposure. Cell-based ELISA and Western blot analysis revealed that AE abolished cisplatin-triggered activation of extracellular signal-regulated kinase (ERK) in tumor cells, while activation of c-Jun N-terminal kinase was not significantly altered. A selective blockade of ERK activation with PD98059 mimicked the protective effect of AE treatment in both tumor cell lines. Moreover, AE failed to protect tumor cells against the ERK-independent toxicity of the Pt(IV)-based complex tetrachloro(O,O-dibutyl-ethylenediamine-N,N'-di-3-propanoate)platinum(IV). Taken together, these data indicate that herbal anthraquinone AE can downregulate the anticancer activity of cisplatin by blocking the activation of ERK in tumor cells.
PB  - New York: Springer
T2  - Cellular and Molecular Life Sciences
T1  - Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin
VL  - 62
DO  - 10.1007/s00018-005-5041-3
SP  - 1275
EP  - 1282
ER  - 

@article{
author = "Mijatović, Sanja and Maksimović-Ivanić, Danijela and Radović, Julijana and Miljković, Đorđe and Kaluđerović, Goran N. and Sabo, Tibor J and Trajković, Vladimir",
year = "2005",
abstract = "The present study describes the ability of an anthraquinone derivative aloe emodin (AE) to reduce the cytotoxic activity of the platinum(II)-based anticancer agent cisplatin toward murine L929 fibrosarcoma and C6 glioma cell lines. The protective effect of AE was demonstrated by MTT and crystal violet assays for cell viability, and involved supression of cisplatin-induced apoptosis and necrosis, as assessed by lactate dehydrogenase release and flow cytometric analysis of DNA fragmentation or phosphatidylserine exposure. Cell-based ELISA and Western blot analysis revealed that AE abolished cisplatin-triggered activation of extracellular signal-regulated kinase (ERK) in tumor cells, while activation of c-Jun N-terminal kinase was not significantly altered. A selective blockade of ERK activation with PD98059 mimicked the protective effect of AE treatment in both tumor cell lines. Moreover, AE failed to protect tumor cells against the ERK-independent toxicity of the Pt(IV)-based complex tetrachloro(O,O-dibutyl-ethylenediamine-N,N'-di-3-propanoate)platinum(IV). Taken together, these data indicate that herbal anthraquinone AE can downregulate the anticancer activity of cisplatin by blocking the activation of ERK in tumor cells.",
publisher = "New York: Springer",
journal = "Cellular and Molecular Life Sciences",
title = "Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin",
volume = "62",
doi = "10.1007/s00018-005-5041-3",
pages = "1275-1282"
}

Mijatović, S., Maksimović-Ivanić, D., Radović, J., Miljković, Đ., Kaluđerović, G. N., Sabo, T. J.,& Trajković, V.. (2005). Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin. in Cellular and Molecular Life Sciences
New York: Springer., 62, 1275-1282.
https://doi.org/10.1007/s00018-005-5041-3

Mijatović S, Maksimović-Ivanić D, Radović J, Miljković Đ, Kaluđerović GN, Sabo TJ, Trajković V. Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin. in Cellular and Molecular Life Sciences. 2005;62:1275-1282.
doi:10.1007/s00018-005-5041-3 .

Mijatović, Sanja, Maksimović-Ivanić, Danijela, Radović, Julijana, Miljković, Đorđe, Kaluđerović, Goran N., Sabo, Tibor J, Trajković, Vladimir, "Aloe emodin decreases the ERK-dependent anticancer activity of cisplatin" in Cellular and Molecular Life Sciences, 62 (2005):1275-1282,
https://doi.org/10.1007/s00018-005-5041-3 . .