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Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells
dc.creator | Mijatović, Sanja | |
dc.creator | Maksimović-Ivanić, Danijela | |
dc.creator | Mojić, Marija | |
dc.creator | Timotijević, Gordana S | |
dc.creator | Miljković, Đorđe | |
dc.creator | Mangano, Katia | |
dc.creator | Donia, Marco | |
dc.creator | Di Cataldo, Antonio | |
dc.creator | Al-Abed, Yousef | |
dc.creator | Cheng, Kai Fan | |
dc.creator | Stošić-Grujičić, Stanislava | |
dc.creator | Nicoletti, Ferdinando | |
dc.date.accessioned | 2017-11-23T11:08:36Z | |
dc.date.available | 2015-11-17T10:26:51Z | |
dc.date.issued | 2011 | sr |
dc.identifier.issn | 0021-9541 | sr |
dc.identifier.other | Rad_konverzija_3278 | sr |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/1283 | |
dc.description.abstract | We have recently shown that covalent attachment of the NO moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties and reduced toxicity. In this study we evaluated the impact of Saq-NO on the growth of A375 human melanoma cells, as a prototype of NO-dependent cancer model. The novel compound strongly affected the in vitro and in vivo progression of A375 melanoma cell growth. The mechanism of antimelanoma action comprised dual drug activity-induction of apoptotic cell death and acquisition of melanoma cell responsiveness to TRAIL. Saq-NO-triggered apoptosis was dependent on transient AKT up-regulation and reduced pERK and iNOS expression that were observed within the first 12 h of exposure to the drug. Thereafter, however, Saq-NO up-regulated both iNOS transcription and NO endogenous synthesis and sensitized A375 cells to TRAIL. Furthermore, reduced YY1 expression was observed after 24 h of Saq-NO exposure, which correlated with increased expression of DR5. The biological relevance of this complex and powerful action of Saq-NO was consistent with the marked drug-induced inhibition of the growth of A375 xenotransplants in nude mice. J. Cell. Physiol. 226: 1803-1812, 2011. (C) 2010 Wiley-Liss, Inc. | en |
dc.description.sponsorship | Serbian Ministry of Science [143029] | sr |
dc.language.iso | English | sr |
dc.rights | restrictedAccess | |
dc.source | Journal of Cellular Physiology | sr |
dc.title | Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Мојић, Марија К.; Ди Цаталдо, Aнтонио; Максимовић-Иванић, Данијела Д.; Мијатовић, Сања A.; Дониа, Марцо; Мангано, Катиа; Цхенг, Каи Фан; Тимотијевић, Гордана С; Ницолетти, Фердинандо; Стошић-Грујичић, Станислава Д.; Миљковић, Ђорђе М.; Aл-Aбед, Yоусеф; | |
dc.citation.issue | 7 | sr |
dc.citation.volume | 226 | sr |
dc.citation.epage | 1812 | sr |
dc.type.version | publishedVersion | en |
dc.citation.rank | M21 | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_ibiss_1283 |
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