Document Detail

Cytotoxic and immune-sensitizing properties of nitric oxide-modified saquinavir in iNOS-positive human melanoma cells.
MedLine Citation:
PMID:  21069718     Owner:  NLM     Status:  Publisher    
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 vitro 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 hours 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. © 2010 Wiley-Liss, Inc.
Sanja Mijatovic; Danijela Maksimovic-Ivanic; Marija Mojic; Gordana Timotijevic; Djordje Miljkovic; Katia Mangano; Marco Donia; Antonio Di Cataldo; Yousef Al-Abed; Kai Fan Cheng; Stanislava Stosic-Grujicic; Ferdinando Nicoletti
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-11-10
Journal Detail:
Title:  Journal of cellular physiology     Volume:  -     ISSN:  1097-4652     ISO Abbreviation:  -     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Immunology, Institute for Biological Research "Sinisa Stankovic", Belgrade University, Belgrade, Serbia.
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