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  - Lazarević, Milica
AU  - Mazzon, Emanuela
AU  - Momčilović, Miljana
AU  - Basile, Maria Sofia
AU  - Colletti, Giuseppe
AU  - Petralia, Maria Cristina
AU  - Bramanti, Placido
AU  - Nicoletti, Ferdinando
AU  - Miljković, Đorđe
PY  - 2018
UR  - http://www.mdpi.com/1420-3049/23/11/2966
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3191
AB  - GYY4137 is a hydrogen sulfide (H₂S) donor that has been shown to act in an anti-inflammatory manner in vitro and in vivo. Microglial cells are among the major players in immunoinflammatory, degenerative, and neoplastic disorders of the central nervous system, including multiple sclerosis, Parkinson's disease, Alzheimer's disease, and glioblastoma multiforme. So far, the effects of GYY4137 on microglial cells have not been thoroughly investigated. In this study, BV2 microglial cells were stimulated with interferon-gamma and lipopolysaccharide and treated with GYY4137. The agent did not influence the viability of BV2 cells in concentrations up to 200 μM. It inhibited tumor necrosis factor but not interleukin-6 production. Expression of CD40 and CD86 were reduced under the influence of the donor. The phagocytic ability of BV2 cells and nitric oxide production were also affected by the agent. Surprisingly, GYY4137 upregulated generation of reactive oxygen species (ROS) by BV2 cells. The effect was mimicked by another H₂S donor, Na₂S, and it was not reproduced in macrophages. Our results demonstrate that GYY4137 downregulates inflammatory properties of BV2 cells but increases their ability to generate ROS. Further investigation of this unexpected phenomenon is warranted.
T2  - Molecules (Basel, Switzerland)
T1  - The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.
IS  - 11
VL  - 23
DO  - 10.3390/molecules23112966
SP  - 2966
ER  - 

@article{
author = "Lazarević, Milica and Mazzon, Emanuela and Momčilović, Miljana and Basile, Maria Sofia and Colletti, Giuseppe and Petralia, Maria Cristina and Bramanti, Placido and Nicoletti, Ferdinando and Miljković, Đorđe",
year = "2018",
abstract = "GYY4137 is a hydrogen sulfide (H₂S) donor that has been shown to act in an anti-inflammatory manner in vitro and in vivo. Microglial cells are among the major players in immunoinflammatory, degenerative, and neoplastic disorders of the central nervous system, including multiple sclerosis, Parkinson's disease, Alzheimer's disease, and glioblastoma multiforme. So far, the effects of GYY4137 on microglial cells have not been thoroughly investigated. In this study, BV2 microglial cells were stimulated with interferon-gamma and lipopolysaccharide and treated with GYY4137. The agent did not influence the viability of BV2 cells in concentrations up to 200 μM. It inhibited tumor necrosis factor but not interleukin-6 production. Expression of CD40 and CD86 were reduced under the influence of the donor. The phagocytic ability of BV2 cells and nitric oxide production were also affected by the agent. Surprisingly, GYY4137 upregulated generation of reactive oxygen species (ROS) by BV2 cells. The effect was mimicked by another H₂S donor, Na₂S, and it was not reproduced in macrophages. Our results demonstrate that GYY4137 downregulates inflammatory properties of BV2 cells but increases their ability to generate ROS. Further investigation of this unexpected phenomenon is warranted.",
journal = "Molecules (Basel, Switzerland)",
title = "The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.",
number = "11",
volume = "23",
doi = "10.3390/molecules23112966",
pages = "2966"
}

Lazarević, M., Mazzon, E., Momčilović, M., Basile, M. S., Colletti, G., Petralia, M. C., Bramanti, P., Nicoletti, F.,& Miljković, Đ.. (2018). The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.. in Molecules (Basel, Switzerland), 23(11), 2966.
https://doi.org/10.3390/molecules23112966

Lazarević M, Mazzon E, Momčilović M, Basile MS, Colletti G, Petralia MC, Bramanti P, Nicoletti F, Miljković Đ. The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide.. in Molecules (Basel, Switzerland). 2018;23(11):2966.
doi:10.3390/molecules23112966 .

Lazarević, Milica, Mazzon, Emanuela, Momčilović, Miljana, Basile, Maria Sofia, Colletti, Giuseppe, Petralia, Maria Cristina, Bramanti, Placido, Nicoletti, Ferdinando, Miljković, Đorđe, "The H₂S Donor GYY4137 Stimulates Reactive Oxygen Species Generation in BV2 Cells While Suppressing the Secretion of TNF and Nitric Oxide." in Molecules (Basel, Switzerland), 23, no. 11 (2018):2966,
https://doi.org/10.3390/molecules23112966 . .

TY  - JOUR
AU  - Basile, Maria Sofia
AU  - Mazzon, Emanuela
AU  - Krajnović, Tamara
AU  - Drača, Dijana
AU  - Cavalli, Eugenio
AU  - Al-Abed, Yousef
AU  - Bramanti, Placido
AU  - Nicoletti, Ferdinando
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2018
UR  - internal-pdf://Basile et al. - 2018 - Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells.pdf
UR  - http://www.mdpi.com/1420-3049/23/10/2463
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6222694
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3216
AB  - Glioblastoma (GBM) is the most frequent and deadly form of primary malignant brain tumor among adults. A promising emerging approach for GBM treatment may be offered from HIV protease inhibitors (HIV-PIs). In fact, in addition to their primary pharmacological activity in the treatment of HIV infection, they possess important anti-neoplastic effects. According to previous studies, the addition of a nitric oxide (NO) donating group to parental compounds can reduce their toxicity and enhance the anticancer action of various compounds, including HIV-PIs. In this study we compared the effects of the HIV-PI Lopinavir (Lopi) and of its NO-derivative Lopinavir-NO (Lopi-NO) on the in vitro growth of LN-229 and U-251 human GBM cell lines. Lopi-NO reduced the viability of LN-229 and U-251 cells at significantly lower concentrations than the parental drug. In particular, Lopi-NO inhibited tumor cell proliferation and induced the differentiation of U-251 cells toward an astrocyte-like phenotype without triggering significant cell death in both cell types. The anticancer effect of Lopi-NO was persistent even upon drug removal. Furthermore, Lopi-NO induced strong autophagy that did not appear to be related to its chemotherapeutic action. Overall, our results suggest that Lopi-NO could be a potential effective anticancer drug for GBM treatment.
T2  - Molecules (Basel, Switzerland)
T2  - Molecules (Basel, Switzerland)
T1  - Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells.
IS  - 10
VL  - 23
DO  - 10.3390/molecules23102463
SP  - 2463
ER  - 

@article{
author = "Basile, Maria Sofia and Mazzon, Emanuela and Krajnović, Tamara and Drača, Dijana and Cavalli, Eugenio and Al-Abed, Yousef and Bramanti, Placido and Nicoletti, Ferdinando and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2018",
abstract = "Glioblastoma (GBM) is the most frequent and deadly form of primary malignant brain tumor among adults. A promising emerging approach for GBM treatment may be offered from HIV protease inhibitors (HIV-PIs). In fact, in addition to their primary pharmacological activity in the treatment of HIV infection, they possess important anti-neoplastic effects. According to previous studies, the addition of a nitric oxide (NO) donating group to parental compounds can reduce their toxicity and enhance the anticancer action of various compounds, including HIV-PIs. In this study we compared the effects of the HIV-PI Lopinavir (Lopi) and of its NO-derivative Lopinavir-NO (Lopi-NO) on the in vitro growth of LN-229 and U-251 human GBM cell lines. Lopi-NO reduced the viability of LN-229 and U-251 cells at significantly lower concentrations than the parental drug. In particular, Lopi-NO inhibited tumor cell proliferation and induced the differentiation of U-251 cells toward an astrocyte-like phenotype without triggering significant cell death in both cell types. The anticancer effect of Lopi-NO was persistent even upon drug removal. Furthermore, Lopi-NO induced strong autophagy that did not appear to be related to its chemotherapeutic action. Overall, our results suggest that Lopi-NO could be a potential effective anticancer drug for GBM treatment.",
journal = "Molecules (Basel, Switzerland), Molecules (Basel, Switzerland)",
title = "Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells.",
number = "10",
volume = "23",
doi = "10.3390/molecules23102463",
pages = "2463"
}

Basile, M. S., Mazzon, E., Krajnović, T., Drača, D., Cavalli, E., Al-Abed, Y., Bramanti, P., Nicoletti, F., Mijatović, S.,& Maksimović-Ivanić, D.. (2018). Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells.. in Molecules (Basel, Switzerland), 23(10), 2463.
https://doi.org/10.3390/molecules23102463

Basile MS, Mazzon E, Krajnović T, Drača D, Cavalli E, Al-Abed Y, Bramanti P, Nicoletti F, Mijatović S, Maksimović-Ivanić D. Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells.. in Molecules (Basel, Switzerland). 2018;23(10):2463.
doi:10.3390/molecules23102463 .

Basile, Maria Sofia, Mazzon, Emanuela, Krajnović, Tamara, Drača, Dijana, Cavalli, Eugenio, Al-Abed, Yousef, Bramanti, Placido, Nicoletti, Ferdinando, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Anticancer and Differentiation Properties of the Nitric Oxide Derivative of Lopinavir in Human Glioblastoma Cells." in Molecules (Basel, Switzerland), 23, no. 10 (2018):2463,
https://doi.org/10.3390/molecules23102463 . .