@article{
author = "Mijatović, Sanja and Maksimović-Ivanić, Danijela and Mojić, Marija and Timotijević, Gordana S and Miljković, Đorđe and Mangano, Katia and Donia, Marco and Di Cataldo, Antonio and Al-Abed, Yousef and Cheng, Kai Fan and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2011",
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.",
journal = "Journal of Cellular Physiology",
title = "Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells",
number = "7",
volume = "226",
pages = "1812",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1283"
}