dc.creator | Paskaš, Svetlana | |
dc.creator | Mazzon, Emanuela | |
dc.creator | Basile, Maria Sofia | |
dc.creator | Cavalli, Eugenio | |
dc.creator | Al-Abed, Yousef | |
dc.creator | He, Mingzhu | |
dc.creator | Rakočević, Sara | |
dc.creator | Nicoletti, Ferdinando | |
dc.creator | Mijatović, Sanja | |
dc.creator | Maksimović-Ivanić, Danijela | |
dc.date.accessioned | 2019-02-22T10:02:43Z | |
dc.date.available | 2900-01-01 | |
dc.date.issued | 2019 | |
dc.identifier.uri | http://link.springer.com/10.1007/s10637-019-00733-3 | |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/3261 | |
dc.description.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. | en |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173013/RS// | |
dc.relation | IRCCS Centro Neurolesi “Bonino–Pulejo”, Messina, Italy | |
dc.rights | restrictedAccess | |
dc.source | Investigational New Drugs | |
dc.subject | HIV protease inhibitors | |
dc.subject | Lopinavir | |
dc.subject | Melanoma | |
dc.subject | Nitric oxide | |
dc.subject | Schwann-like cells | |
dc.subject | Trans-differentiation | |
dc.title | Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo. | en |
dc.type | article | en |
dc.rights.license | ARR | |
dcterms.abstract | Цавалли, Еугенио; Паскаш, Светлана; Маззон, Емануела; Басиле, Мариа Софиа; Aл-Aбед, Yоусеф; Хе, Мингзху; Ницолетти, Фердинандо; Мијатовић, Сања; Максимовић-Иванић, Данијела; Ракочевић, Сара; | |
dc.rights.holder | © 2019, Springer Science+Business Media, LLC, part of Springer Nature. | |
dc.identifier.doi | 10.1007/s10637-019-00733-3 | |
dc.identifier.pmid | 30706336 | |
dc.identifier.scopus | 2-s2.0-85060929429 | |
dc.identifier.wos | 000486034100020 | |
dc.citation.apa | Paskas, S., Mazzon, E., Basile, M. S., Cavalli, E., Al-Abed, Y., He, M., … Maksimovic-Ivanic, D. (2019). Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo. Investigational New Drugs, DOI:10.1007/s10637-019-00733-3. | |
dc.citation.vancouver | Paskas S, Mazzon E, Basile MS, Cavalli E, Al-Abed Y, He M, Rakocevic S, Nicoletti F, Mijatovic S, Maksimovic-Ivanic D. Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo. Invest New Drugs. 2019;DOI:10.1007/s10637-019-00733-3. | |
dc.type.version | acceptedVersion | |
dc.citation.rank | M21 | |