TY  - JOUR
AU  - Paskaš, Svetlana
AU  - Mazzon, Emanuela
AU  - Basile, Maria Sofia
AU  - Cavalli, Eugenio
AU  - Al-Abed, Yousef
AU  - He, Mingzhu
AU  - Rakočević, Sara
AU  - Nicoletti, Ferdinando
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2019
UR  - http://link.springer.com/10.1007/s10637-019-00733-3
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3261
AB  - We generated a nitric oxide (NO)-releasing derivative of the anti-HIV protease inhibitor lopinavir by linking the NO moiety to the parental drug. We investigated the effects of lopinavir and its derivative lopinavir-NO on melanoma cell lines in vitro and in vivo. Lopinavir-NO exhibited a twofold stronger anticancer action than lopinavir in vitro. These results were successfully translated into syngeneic models of melanoma in vivo, where a significant reduction in tumour volume was observed only in animals treated with lopinavir-NO. Both lopinavir and lopinavir-NO inhibited cell proliferation and induced the trans-differentiation of melanoma cells to Schwann-like cells. In melanoma cancer cell lines, both lopinavir and lopinavir-NO induced morphological changes, minor apoptosis and reactive oxygen species (ROS) production. However, caspase activation and autophagy were detected only in B16 cells, indicating a cell line-specific treatment response. Lopinavir-NO released NO intracellularly, and NO neutralization restored cell viability. Treatment with lopinavir-NO induced only a transient activation of Akt and inhibition of P70S6 kinase. The results of this study identify lopinavir-NO as a promising candidate for further clinical trials in melanoma and possibly other solid tumours.
T2  - Investigational New Drugs
T1  - Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo.
DO  - 10.1007/s10637-019-00733-3
ER  - 

@article{
author = "Paskaš, Svetlana and Mazzon, Emanuela and Basile, Maria Sofia and Cavalli, Eugenio and Al-Abed, Yousef and He, Mingzhu and Rakočević, Sara and Nicoletti, Ferdinando and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2019",
abstract = "We generated a nitric oxide (NO)-releasing derivative of the anti-HIV protease inhibitor lopinavir by linking the NO moiety to the parental drug. We investigated the effects of lopinavir and its derivative lopinavir-NO on melanoma cell lines in vitro and in vivo. Lopinavir-NO exhibited a twofold stronger anticancer action than lopinavir in vitro. These results were successfully translated into syngeneic models of melanoma in vivo, where a significant reduction in tumour volume was observed only in animals treated with lopinavir-NO. Both lopinavir and lopinavir-NO inhibited cell proliferation and induced the trans-differentiation of melanoma cells to Schwann-like cells. In melanoma cancer cell lines, both lopinavir and lopinavir-NO induced morphological changes, minor apoptosis and reactive oxygen species (ROS) production. However, caspase activation and autophagy were detected only in B16 cells, indicating a cell line-specific treatment response. Lopinavir-NO released NO intracellularly, and NO neutralization restored cell viability. Treatment with lopinavir-NO induced only a transient activation of Akt and inhibition of P70S6 kinase. The results of this study identify lopinavir-NO as a promising candidate for further clinical trials in melanoma and possibly other solid tumours.",
journal = "Investigational New Drugs",
title = "Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo.",
doi = "10.1007/s10637-019-00733-3"
}

Paskaš, S., Mazzon, E., Basile, M. S., Cavalli, E., Al-Abed, Y., He, M., Rakočević, S., Nicoletti, F., Mijatović, S.,& Maksimović-Ivanić, D.. (2019). Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo.. in Investigational New Drugs.
https://doi.org/10.1007/s10637-019-00733-3

Paskaš S, Mazzon E, Basile MS, Cavalli E, Al-Abed Y, He M, Rakočević S, Nicoletti F, Mijatović S, Maksimović-Ivanić D. Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo.. in Investigational New Drugs. 2019;.
doi:10.1007/s10637-019-00733-3 .

Paskaš, Svetlana, Mazzon, Emanuela, Basile, Maria Sofia, Cavalli, Eugenio, Al-Abed, Yousef, He, Mingzhu, Rakočević, Sara, Nicoletti, Ferdinando, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo." in Investigational New Drugs (2019),
https://doi.org/10.1007/s10637-019-00733-3 . .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Nikolić, Ivana
AU  - Krajnović, Tamara
AU  - Cheng, Kai-Fan
AU  - VanPatten, Sonya
AU  - He, Mingzhu
AU  - Stošić-Grujičić, Stanislava
AU  - Stojanović, Ivana D.
AU  - Al-Abed, Yousef
AU  - Saksida, Tamara
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2141
AB  - Macrophage migration inhibitory factor is a multifunctional cytokine
   involved in the regulation of immune processes and also in apoptosis
   induction. Elevated MIF expression is detrimental for insulin-producing
   beta cells and MIF inhibition protected beta cells from several
   cytotoxic insults such as inflammatory cytokines, high fatty acids or
   high glucose concentrations. Therefore, the aim of this study was to
   investigate two newly synthesized small molecule MIF inhibitors (K664-1
   and K647-1) and to compare them with previously established effects of
   the prototypical MIF inhibitor, ISO-1. Our results indicate that K664-1
   and K647-1 are 160- and 40-fold more effective in inhibition of MIF's
   tautomerase activity than ISO-1. Also, new inhibitors confer beta cell
   protection from cytokine-triggered apoptosis at significantly lower
   concentrations than LSO-1. Although all three MIF inhibitors inhibit
   caspase 3 activity, K664-1 and K647-1 suppress pro-apoptotic BAX protein
   expression and up-regulate anti-apoptotic Bcl-2 mRNA. Finally, all three
   MIF inhibitors operate through blockade of nitric oxide production
   stimulated by cytokines. In conclusion, two novel MIF inhibitors are
   more potent than ISO-1 and operate through inhibition of the
   mitochondria-related apoptotic pathway. We propose that these compounds
   represent a unique class of anti-MIF antagonists that should be further
   tested for therapeutic use. (C) 2014 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death
VL  - 740
DO  - 10.1016/j.ejphar.2014.06.009
SP  - 683
EP  - 689
ER  - 

@article{
author = "Vujičić, Milica and Nikolić, Ivana and Krajnović, Tamara and Cheng, Kai-Fan and VanPatten, Sonya and He, Mingzhu and Stošić-Grujičić, Stanislava and Stojanović, Ivana D. and Al-Abed, Yousef and Saksida, Tamara",
year = "2014",
abstract = "Macrophage migration inhibitory factor is a multifunctional cytokine
   involved in the regulation of immune processes and also in apoptosis
   induction. Elevated MIF expression is detrimental for insulin-producing
   beta cells and MIF inhibition protected beta cells from several
   cytotoxic insults such as inflammatory cytokines, high fatty acids or
   high glucose concentrations. Therefore, the aim of this study was to
   investigate two newly synthesized small molecule MIF inhibitors (K664-1
   and K647-1) and to compare them with previously established effects of
   the prototypical MIF inhibitor, ISO-1. Our results indicate that K664-1
   and K647-1 are 160- and 40-fold more effective in inhibition of MIF's
   tautomerase activity than ISO-1. Also, new inhibitors confer beta cell
   protection from cytokine-triggered apoptosis at significantly lower
   concentrations than LSO-1. Although all three MIF inhibitors inhibit
   caspase 3 activity, K664-1 and K647-1 suppress pro-apoptotic BAX protein
   expression and up-regulate anti-apoptotic Bcl-2 mRNA. Finally, all three
   MIF inhibitors operate through blockade of nitric oxide production
   stimulated by cytokines. In conclusion, two novel MIF inhibitors are
   more potent than ISO-1 and operate through inhibition of the
   mitochondria-related apoptotic pathway. We propose that these compounds
   represent a unique class of anti-MIF antagonists that should be further
   tested for therapeutic use. (C) 2014 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death",
volume = "740",
doi = "10.1016/j.ejphar.2014.06.009",
pages = "683-689"
}

Vujičić, M., Nikolić, I., Krajnović, T., Cheng, K., VanPatten, S., He, M., Stošić-Grujičić, S., Stojanović, I. D., Al-Abed, Y.,& Saksida, T.. (2014). Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death. in European Journal of Pharmacology, 740, 683-689.
https://doi.org/10.1016/j.ejphar.2014.06.009

Vujičić M, Nikolić I, Krajnović T, Cheng K, VanPatten S, He M, Stošić-Grujičić S, Stojanović ID, Al-Abed Y, Saksida T. Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death. in European Journal of Pharmacology. 2014;740:683-689.
doi:10.1016/j.ejphar.2014.06.009 .

Vujičić, Milica, Nikolić, Ivana, Krajnović, Tamara, Cheng, Kai-Fan, VanPatten, Sonya, He, Mingzhu, Stošić-Grujičić, Stanislava, Stojanović, Ivana D., Al-Abed, Yousef, Saksida, Tamara, "Novel inhibitors of macrophage migration inhibitory factor prevent
 cytokine-induced beta cell death" in European Journal of Pharmacology, 740 (2014):683-689,
https://doi.org/10.1016/j.ejphar.2014.06.009 . .