Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells
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2011
Authors
Mijatović, SanjaMaksimović-Ivanić, Danijela
Mojić, Marija
Timotijević, Gordana
Miljković, Djordje
Mangano, Katia
Donia, Marco
Di Cataldo, Antonio
Al-Abed, Yousef
Cheng, Kai Fan
Stošić-Grujičić, Stanislava
Nicoletti, Ferdinando
Article (Published version)
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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 af...ter 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.
Source:
Journal of Cellular Physiology, 2011, 226, 7, 1803-1812Publisher:
- Wiley, Hoboken
Funding / projects:
- Fiziološka i farmakološka modulacija imunoinflamatornih i malignih bolesti (RS-MESTD-MPN2006-2010-143029)
DOI: 10.1002/jcp.22513
ISSN: 0021-9541
PubMed: 21506111
WoS: 000290519900013
Scopus: 2-s2.0-79955042497
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Mijatović, Sanja AU - Maksimović-Ivanić, Danijela AU - Mojić, Marija AU - Timotijević, Gordana AU - Miljković, Djordje AU - Mangano, Katia AU - Donia, Marco AU - Di Cataldo, Antonio AU - Al-Abed, Yousef AU - Cheng, Kai Fan AU - Stošić-Grujičić, Stanislava AU - Nicoletti, Ferdinando PY - 2011 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/533 AB - 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. PB - Wiley, Hoboken T2 - Journal of Cellular Physiology T1 - Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells EP - 1812 IS - 7 SP - 1803 VL - 226 DO - 10.1002/jcp.22513 ER -
@article{ author = "Mijatović, Sanja and Maksimović-Ivanić, Danijela and Mojić, Marija and Timotijević, Gordana and Miljković, Djordje 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.", publisher = "Wiley, Hoboken", journal = "Journal of Cellular Physiology", title = "Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells", pages = "1812-1803", number = "7", volume = "226", doi = "10.1002/jcp.22513" }
Mijatović, S., Maksimović-Ivanić, D., Mojić, M., Timotijević, G., Miljković, D., Mangano, K., Donia, M., Di Cataldo, A., Al-Abed, Y., Cheng, K. F., Stošić-Grujičić, S.,& Nicoletti, F.. (2011). Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells. in Journal of Cellular Physiology Wiley, Hoboken., 226(7), 1803-1812. https://doi.org/10.1002/jcp.22513
Mijatović S, Maksimović-Ivanić D, Mojić M, Timotijević G, Miljković D, Mangano K, Donia M, Di Cataldo A, Al-Abed Y, Cheng KF, Stošić-Grujičić S, Nicoletti F. Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells. in Journal of Cellular Physiology. 2011;226(7):1803-1812. doi:10.1002/jcp.22513 .
Mijatović, Sanja, Maksimović-Ivanić, Danijela, Mojić, Marija, Timotijević, Gordana, Miljković, Djordje, Mangano, Katia, Donia, Marco, Di Cataldo, Antonio, Al-Abed, Yousef, Cheng, Kai Fan, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "Cytotoxic and Immune-Sensitizing Properties of Nitric Oxide-Modified Saquinavir in iNOS-Positive Human Melanoma Cells" in Journal of Cellular Physiology, 226, no. 7 (2011):1803-1812, https://doi.org/10.1002/jcp.22513 . .