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 . .