TY  - JOUR
AU  - Paskaš, Svetlana
AU  - Krajnović, Tamara
AU  - Basile, Maria S.
AU  - Dunđerović, Duško
AU  - Cavalli, Eugenio
AU  - Mangano, Katia
AU  - Mammana, Santa
AU  - Al-Abed, Yousef
AU  - Nicoletti, Ferdinando
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2019
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/mc.23020
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3339
AB  - The main focus of this study is exploring the effect and mechanism of two HIV-protease inhibitors: Ritonavir and Ritonavir-nitric oxide (Ritonavir-NO) on in vitro growth of melanoma cell lines. NO modification significantly improved the antitumor potential of Ritonavir, as the IC50 values of Ritonavir-NO were approximately two times lower than IC50 values of the parental compound. Our results showed for the first time, that both compounds induced senescence in primary and metastatic melanoma cell lines. This transformation was manifested as a change in cell morphology, enlargement of nuclei, increased cellular granulation, upregulation of β-galactosidase activity, lipofuscin granules appearance, higher production of reactive oxygen species and persistent inhibition of proliferation. The expression of p53, as one of the key regulators of senescence, was upregulated after 48 hours of Ritonavir-NO treatment only in metastatic B16F10 cells, ranking it as a late-response event. The development of senescent phenotype was consistent with the alteration of the cytoskeleton-as we observed diminished expression of vinculin, α-actin, and β-tubulin. Permanent inhibition of S6 protein by Ritonavir-NO, but not Ritonavir, could be responsible for a stronger antiproliferative potential of the NO-modified compound. Taken together, induction of senescent phenotype may provide an excellent platform for developing therapeutic approaches based on selective killing of senescent cells.
T2  - Molecular Carcinogenesis
T2  - Molecular Carcinogenesis
T1  - Senescence as a main mechanism of Ritonavir and Ritonavir-NO action against melanoma.
DO  - 10.1002/mc.23020
ER  - 

@article{
author = "Paskaš, Svetlana and Krajnović, Tamara and Basile, Maria S. and Dunđerović, Duško and Cavalli, Eugenio and Mangano, Katia and Mammana, Santa and Al-Abed, Yousef and Nicoletti, Ferdinando and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2019",
abstract = "The main focus of this study is exploring the effect and mechanism of two HIV-protease inhibitors: Ritonavir and Ritonavir-nitric oxide (Ritonavir-NO) on in vitro growth of melanoma cell lines. NO modification significantly improved the antitumor potential of Ritonavir, as the IC50 values of Ritonavir-NO were approximately two times lower than IC50 values of the parental compound. Our results showed for the first time, that both compounds induced senescence in primary and metastatic melanoma cell lines. This transformation was manifested as a change in cell morphology, enlargement of nuclei, increased cellular granulation, upregulation of β-galactosidase activity, lipofuscin granules appearance, higher production of reactive oxygen species and persistent inhibition of proliferation. The expression of p53, as one of the key regulators of senescence, was upregulated after 48 hours of Ritonavir-NO treatment only in metastatic B16F10 cells, ranking it as a late-response event. The development of senescent phenotype was consistent with the alteration of the cytoskeleton-as we observed diminished expression of vinculin, α-actin, and β-tubulin. Permanent inhibition of S6 protein by Ritonavir-NO, but not Ritonavir, could be responsible for a stronger antiproliferative potential of the NO-modified compound. Taken together, induction of senescent phenotype may provide an excellent platform for developing therapeutic approaches based on selective killing of senescent cells.",
journal = "Molecular Carcinogenesis, Molecular Carcinogenesis",
title = "Senescence as a main mechanism of Ritonavir and Ritonavir-NO action against melanoma.",
doi = "10.1002/mc.23020"
}

Paskaš, S., Krajnović, T., Basile, M. S., Dunđerović, D., Cavalli, E., Mangano, K., Mammana, S., Al-Abed, Y., Nicoletti, F., Mijatović, S.,& Maksimović-Ivanić, D.. (2019). Senescence as a main mechanism of Ritonavir and Ritonavir-NO action against melanoma.. in Molecular Carcinogenesis.
https://doi.org/10.1002/mc.23020

Paskaš S, Krajnović T, Basile MS, Dunđerović D, Cavalli E, Mangano K, Mammana S, Al-Abed Y, Nicoletti F, Mijatović S, Maksimović-Ivanić D. Senescence as a main mechanism of Ritonavir and Ritonavir-NO action against melanoma.. in Molecular Carcinogenesis. 2019;.
doi:10.1002/mc.23020 .

Paskaš, Svetlana, Krajnović, Tamara, Basile, Maria S., Dunđerović, Duško, Cavalli, Eugenio, Mangano, Katia, Mammana, Santa, Al-Abed, Yousef, Nicoletti, Ferdinando, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Senescence as a main mechanism of Ritonavir and Ritonavir-NO action against melanoma." in Molecular Carcinogenesis (2019),
https://doi.org/10.1002/mc.23020 . .

TY  - JOUR
AU  - Momčilović, Miljana
AU  - Mangano, Katia
AU  - Jevtić, Bojan
AU  - Mammana, Santa
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
AU  - Miljković, Đorđe
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2118
AB  - Covalent attachment of the nitric oxide (NO) moiety to the HIV protease
   inhibitor Saquinavir (Saq) produced a new chemical entity, named
   Saquinavir-NO, (Saq-NO) with reduced toxicity and potent
   immunoregulatory influence on T lymphocytes. In this study, we have
   compared head-to-head the effects of Saq-NO and Saq on mouse and rat
   peritoneal macrophage cytokine secretion and NO production upon in
   vitro, ex vivo and in vivo conditions. The results demonstrate that
   Saq-NO, but not Saq, potently decreased interleukin (IL)-10, IL-6 and
   nitrite accumulation and increased the levels of IL-1 and tumour
   necrosis factor (TNF) in supernatants of mouse and rat macrophage
   cultures in vitro. Treatment of mice with Saq-NO, but not Saq, inhibited
   ex vivo secretion of IL-6 from macrophages. Consistent with these
   findings, Saq-NO also reduced blood levels of IL-6 in
   lipopolysaccharide-treated mice. The observed inhibitory influence of
   Saq-NO on IL-6 generation in macrophages may be involved in the observed
   antitumour and immunomodulatory effects of the drug.
T2  - Basic & Clinical Pharmacology & Toxicology
T1  - Saquinavir-NO Inhibits IL-6 Production in Macrophages
IS  - 6
VL  - 115
DO  - 10.1111/bcpt.12268
SP  - 499
EP  - 506
ER  - 

@article{
author = "Momčilović, Miljana and Mangano, Katia and Jevtić, Bojan and Mammana, Santa and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando and Miljković, Đorđe",
year = "2014",
abstract = "Covalent attachment of the nitric oxide (NO) moiety to the HIV protease
   inhibitor Saquinavir (Saq) produced a new chemical entity, named
   Saquinavir-NO, (Saq-NO) with reduced toxicity and potent
   immunoregulatory influence on T lymphocytes. In this study, we have
   compared head-to-head the effects of Saq-NO and Saq on mouse and rat
   peritoneal macrophage cytokine secretion and NO production upon in
   vitro, ex vivo and in vivo conditions. The results demonstrate that
   Saq-NO, but not Saq, potently decreased interleukin (IL)-10, IL-6 and
   nitrite accumulation and increased the levels of IL-1 and tumour
   necrosis factor (TNF) in supernatants of mouse and rat macrophage
   cultures in vitro. Treatment of mice with Saq-NO, but not Saq, inhibited
   ex vivo secretion of IL-6 from macrophages. Consistent with these
   findings, Saq-NO also reduced blood levels of IL-6 in
   lipopolysaccharide-treated mice. The observed inhibitory influence of
   Saq-NO on IL-6 generation in macrophages may be involved in the observed
   antitumour and immunomodulatory effects of the drug.",
journal = "Basic & Clinical Pharmacology & Toxicology",
title = "Saquinavir-NO Inhibits IL-6 Production in Macrophages",
number = "6",
volume = "115",
doi = "10.1111/bcpt.12268",
pages = "499-506"
}

Momčilović, M., Mangano, K., Jevtić, B., Mammana, S., Stošić-Grujičić, S., Nicoletti, F.,& Miljković, Đ.. (2014). Saquinavir-NO Inhibits IL-6 Production in Macrophages. in Basic & Clinical Pharmacology & Toxicology, 115(6), 499-506.
https://doi.org/10.1111/bcpt.12268

Momčilović M, Mangano K, Jevtić B, Mammana S, Stošić-Grujičić S, Nicoletti F, Miljković Đ. Saquinavir-NO Inhibits IL-6 Production in Macrophages. in Basic & Clinical Pharmacology & Toxicology. 2014;115(6):499-506.
doi:10.1111/bcpt.12268 .

Momčilović, Miljana, Mangano, Katia, Jevtić, Bojan, Mammana, Santa, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, Miljković, Đorđe, "Saquinavir-NO Inhibits IL-6 Production in Macrophages" in Basic & Clinical Pharmacology & Toxicology, 115, no. 6 (2014):499-506,
https://doi.org/10.1111/bcpt.12268 . .

TY  - JOUR
AU  - Saksida, Tamara
AU  - Miljković, Đorđe
AU  - Timotijević, Gordana S
AU  - Stojanović, Ivana D.
AU  - Mijatović, Sanja
AU  - Fagone, Paolo
AU  - Mangano, Katia
AU  - Mammana, Santa
AU  - Farina, Claudio
AU  - Ascione, Ester
AU  - Maiello, Valentina
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/965
AB  - Transferrin (Tf) has a major role in T cell activation and proliferation. Here, we investigated whether Tf exerts immunomodulatory effects on T cells and in development of T-cell driven experimental autoimmune encephalomyelitis (EAE). While treatment of concanavalin A-stimulated splenocytes with apotransferrin (ApoTf) did not affect release of IL-1 beta, TNF, INF-gamma, IL-17, IL-4, and IL-10, it markedly and dose-dependently down-regulated synthesis of IL-2 in these cells. ApoTf also inhibited IL-2 generation in purified CD3(+) T cells and the effect was accompanied with down-regulation of MAPK p44/42 and NF kappa B signaling. Despite impeded IL-2 release, proliferation of splenocytes was not inhibited by ApoTf. Importantly, ApoTf ameliorated EAE in mice and significantly reduced ex vivo IL-2 production in proteolipid protein-specific lymphocytes. Thus ApoTf may be a promising beneficial agent for multiple sclerosis. (C) 2013 Elsevier B.V. All rights reserved.
T2  - Journal of Neuroimmunology
T1  - Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis
IS  - 1-2
VL  - 262
SP  - 63
EP  - 78
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_965
ER  - 

@article{
author = "Saksida, Tamara and Miljković, Đorđe and Timotijević, Gordana S and Stojanović, Ivana D. and Mijatović, Sanja and Fagone, Paolo and Mangano, Katia and Mammana, Santa and Farina, Claudio and Ascione, Ester and Maiello, Valentina and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava",
year = "2013",
abstract = "Transferrin (Tf) has a major role in T cell activation and proliferation. Here, we investigated whether Tf exerts immunomodulatory effects on T cells and in development of T-cell driven experimental autoimmune encephalomyelitis (EAE). While treatment of concanavalin A-stimulated splenocytes with apotransferrin (ApoTf) did not affect release of IL-1 beta, TNF, INF-gamma, IL-17, IL-4, and IL-10, it markedly and dose-dependently down-regulated synthesis of IL-2 in these cells. ApoTf also inhibited IL-2 generation in purified CD3(+) T cells and the effect was accompanied with down-regulation of MAPK p44/42 and NF kappa B signaling. Despite impeded IL-2 release, proliferation of splenocytes was not inhibited by ApoTf. Importantly, ApoTf ameliorated EAE in mice and significantly reduced ex vivo IL-2 production in proteolipid protein-specific lymphocytes. Thus ApoTf may be a promising beneficial agent for multiple sclerosis. (C) 2013 Elsevier B.V. All rights reserved.",
journal = "Journal of Neuroimmunology",
title = "Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis",
number = "1-2",
volume = "262",
pages = "63-78",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_965"
}

Saksida, T., Miljković, Đ., Timotijević, G. S., Stojanović, I. D., Mijatović, S., Fagone, P., Mangano, K., Mammana, S., Farina, C., Ascione, E., Maiello, V., Nicoletti, F.,& Stošić-Grujičić, S.. (2013). Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology, 262(1-2), 63-78.
https://hdl.handle.net/21.15107/rcub_ibiss_965

Saksida T, Miljković Đ, Timotijević GS, Stojanović ID, Mijatović S, Fagone P, Mangano K, Mammana S, Farina C, Ascione E, Maiello V, Nicoletti F, Stošić-Grujičić S. Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology. 2013;262(1-2):63-78.
https://hdl.handle.net/21.15107/rcub_ibiss_965 .

Saksida, Tamara, Miljković, Đorđe, Timotijević, Gordana S, Stojanović, Ivana D., Mijatović, Sanja, Fagone, Paolo, Mangano, Katia, Mammana, Santa, Farina, Claudio, Ascione, Ester, Maiello, Valentina, Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, "Apotransferrin inhibits interleukin-2 expression and protects mice from experimental autoimmune encephalomyelitis" in Journal of Neuroimmunology, 262, no. 1-2 (2013):63-78,
https://hdl.handle.net/21.15107/rcub_ibiss_965 .