TY  - CHAP
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Donia, Marco
AU  - Stošić-Grujičić, Stanislava
AU  - Garotta, Gianni
AU  - Al-Abed, Yousef
AU  - Nicoletti, Ferdinando
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3836
AB  - Nonsteroidal-anti-inflammatory drugs modified by covalent attachment of nitric oxide (NO) have been recognized as compounds with antitumor properties. By adopting this approach the new compound GIT-27NO was synthesized at GaNiAl Immunotherapeutics Inc. (Wilmington, Delaware, USA) on the basis of the anti-inflammatory isoxazoline derivative VGX-1027. In contrast to the usual modification, i.e., connection via a spacer molecule, GIT-27NO was generated by direct addition of a releasing NO moiety. Contrary to the parental compound which is completely inefficient as an antitumor drug, the modified compound acquired strong anticancer potential. The drug reduced the growth of various cell lines in vitro as well as some solid localized and even metastatic tumors in vivo. Decreased viability of tumor cells was caused by induction of different types of programmed cell death whereas accidental cell death was a secondary event. The outcome of the drug treatment was independent of the type of intracellular response, since the absence or inactivation of key executive mediators of apoptosis, like p53 or caspases, did not affect the death signal triggered by GIT-27NO. Furthermore, cells made resistant to apoptotic stimuli are sensitive to GIT-27NO as well. Although the drug efficacy is explicitly related to NO liberation, GIT-27NO did not function as a simple exogenous donor. Signal for NO release came from cells, and further events included the generation of ROS, RNS and subsequent nitration of tyrosine residues, caspase inhibition, or decreased activity of the YY1 repressor. The drug effect on the MAP signaling pathway was heterogeneous and defined by the cell specificity, the plasticity of the agent’s action, its high efficacy, and low toxicity and suggests that GIT-27NO is a candidate for anticancer drug of the future.
PB  - New York: Springer
T2  - Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development
T1  - (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid–Nitric Oxide (GIT-27NO) – New Dress for Nitric Oxide Mission
DO  - 10.1007/978-1-4419-1432-3_23
SP  - 443
EP  - 457
ER  - 

@inbook{
author = "Mijatović, Sanja and Maksimović-Ivanić, Danijela and Donia, Marco and Stošić-Grujičić, Stanislava and Garotta, Gianni and Al-Abed, Yousef and Nicoletti, Ferdinando",
year = "2010",
abstract = "Nonsteroidal-anti-inflammatory drugs modified by covalent attachment of nitric oxide (NO) have been recognized as compounds with antitumor properties. By adopting this approach the new compound GIT-27NO was synthesized at GaNiAl Immunotherapeutics Inc. (Wilmington, Delaware, USA) on the basis of the anti-inflammatory isoxazoline derivative VGX-1027. In contrast to the usual modification, i.e., connection via a spacer molecule, GIT-27NO was generated by direct addition of a releasing NO moiety. Contrary to the parental compound which is completely inefficient as an antitumor drug, the modified compound acquired strong anticancer potential. The drug reduced the growth of various cell lines in vitro as well as some solid localized and even metastatic tumors in vivo. Decreased viability of tumor cells was caused by induction of different types of programmed cell death whereas accidental cell death was a secondary event. The outcome of the drug treatment was independent of the type of intracellular response, since the absence or inactivation of key executive mediators of apoptosis, like p53 or caspases, did not affect the death signal triggered by GIT-27NO. Furthermore, cells made resistant to apoptotic stimuli are sensitive to GIT-27NO as well. Although the drug efficacy is explicitly related to NO liberation, GIT-27NO did not function as a simple exogenous donor. Signal for NO release came from cells, and further events included the generation of ROS, RNS and subsequent nitration of tyrosine residues, caspase inhibition, or decreased activity of the YY1 repressor. The drug effect on the MAP signaling pathway was heterogeneous and defined by the cell specificity, the plasticity of the agent’s action, its high efficacy, and low toxicity and suggests that GIT-27NO is a candidate for anticancer drug of the future.",
publisher = "New York: Springer",
journal = "Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development",
booktitle = "(S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid–Nitric Oxide (GIT-27NO) – New Dress for Nitric Oxide Mission",
doi = "10.1007/978-1-4419-1432-3_23",
pages = "443-457"
}

Mijatović, S., Maksimović-Ivanić, D., Donia, M., Stošić-Grujičić, S., Garotta, G., Al-Abed, Y.,& Nicoletti, F.. (2010). (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid–Nitric Oxide (GIT-27NO) – New Dress for Nitric Oxide Mission. in Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development
New York: Springer., 443-457.
https://doi.org/10.1007/978-1-4419-1432-3_23

Mijatović S, Maksimović-Ivanić D, Donia M, Stošić-Grujičić S, Garotta G, Al-Abed Y, Nicoletti F. (S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid–Nitric Oxide (GIT-27NO) – New Dress for Nitric Oxide Mission. in Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development. 2010;:443-457.
doi:10.1007/978-1-4419-1432-3_23 .

Mijatović, Sanja, Maksimović-Ivanić, Danijela, Donia, Marco, Stošić-Grujičić, Stanislava, Garotta, Gianni, Al-Abed, Yousef, Nicoletti, Ferdinando, "(S,R)-3-Phenyl-4,5-dihydro-5-isoxazole acetic acid–Nitric Oxide (GIT-27NO) – New Dress for Nitric Oxide Mission" in Nitric Oxide (NO) and Cancer. Cancer Drug Discovery and Development (2010):443-457,
https://doi.org/10.1007/978-1-4419-1432-3_23 . .

TY  - CONF
AU  - Donia, Marco
AU  - Mijatović, Sanja
AU  - Stošić-Grujičić, Stanislava
AU  - Garotta, Gianni
AU  - Maksimović-Ivanić, Danijela
AU  - Al-Abed, Yousef
AU  - Nicoletti, Ferdinando
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1413
C3  - International Journal of Molecular Medicine
T1  - Generation of new anti-cancer compounds from Nitric Oxide (NO)-hybridization of protease inhibitors. Saquinavir-NO as prototypic example?
IS  - null
VL  - 26
EP  - S65
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1413
ER  - 

@conference{
author = "Donia, Marco and Mijatović, Sanja and Stošić-Grujičić, Stanislava and Garotta, Gianni and Maksimović-Ivanić, Danijela and Al-Abed, Yousef and Nicoletti, Ferdinando",
year = "2010",
journal = "International Journal of Molecular Medicine",
title = "Generation of new anti-cancer compounds from Nitric Oxide (NO)-hybridization of protease inhibitors. Saquinavir-NO as prototypic example?",
number = "null",
volume = "26",
pages = "S65",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1413"
}

Donia, M., Mijatović, S., Stošić-Grujičić, S., Garotta, G., Maksimović-Ivanić, D., Al-Abed, Y.,& Nicoletti, F.. (2010). Generation of new anti-cancer compounds from Nitric Oxide (NO)-hybridization of protease inhibitors. Saquinavir-NO as prototypic example?. in International Journal of Molecular Medicine, 26(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1413

Donia M, Mijatović S, Stošić-Grujičić S, Garotta G, Maksimović-Ivanić D, Al-Abed Y, Nicoletti F. Generation of new anti-cancer compounds from Nitric Oxide (NO)-hybridization of protease inhibitors. Saquinavir-NO as prototypic example?. in International Journal of Molecular Medicine. 2010;26(null):null-S65.
https://hdl.handle.net/21.15107/rcub_ibiss_1413 .

Donia, Marco, Mijatović, Sanja, Stošić-Grujičić, Stanislava, Garotta, Gianni, Maksimović-Ivanić, Danijela, Al-Abed, Yousef, Nicoletti, Ferdinando, "Generation of new anti-cancer compounds from Nitric Oxide (NO)-hybridization of protease inhibitors. Saquinavir-NO as prototypic example?" in International Journal of Molecular Medicine, 26, no. null (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1413 .

TY  - JOUR
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Miljković, Đorđe
AU  - Harhaji-Trajković, Ljubica
AU  - Timotijević, Gordana S
AU  - Mojić, Marija
AU  - Dabideen, Darrin
AU  - Cheng, Kai Fan
AU  - McCubrey, James A
AU  - Mangano, Katia
AU  - Al-Abed, Yousef
AU  - Libra, Massimo
AU  - Garotta, Gianni
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1453
AB  - Application of the HIV protease inhibitor saquinavir (Saq) to cancer chemotherapy is limited by its numerous side effects. To overcome this toxicity, we modified the original compound by covalently attaching a nitric oxide (NO) group. We compared the efficacy of the parental and NO-modified drugs in vitro and in vivo. The novel compound saquinavir-NO (Saq-NO) significantly reduced the viability of a wide spectrum of human and rodent tumor cell lines at significantly lower concentration than the unmodified drug. In contrast to Saq, Saq-NO had no effect on the viability of primary cells and drastically reduced B16 melanoma growth in syngeneic C57BL/6 mice. In addition, at the equivalent of the 100% lethal dose of Saq, Saq-NO treatment caused no apparent signs of toxicity. Saq-NO blocked the proliferation of C6 and 1316 cells, up-regulated p53 expression, and promoted the differentiation of these two cell types into oligodendrocytes or Schwann-like cells, respectively. Although it has been well documented that Saq decreases tumor cell viability by inhibiting Akt, the anticancer properties of Saq-NO were completely independent of the phosphatidylinositol 3-kinase/Akt signaling pathway. Moreover, Saq-NO transiently up-regulated Akt phosphorylation, delivering a protective signal that could be relevant for primary cell protection and the absence of drug toxicity in vivo. It was unlikely that released NO was independently responsible for these drug effects because Saq-NO treatment increased intracellular and secreted NO levels only slightly. Rather, the chemical modification seems to have produced a qualitatively new chemical entity, which may have a unique mode of action against cancer cells. [Mol Cancer Ther 2009;8(5):1169-78]
T2  - Molecular Cancer Therapeutics
T1  - The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt
IS  - 5
VL  - 8
EP  - 1178
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1453
ER  - 

@article{
author = "Maksimović-Ivanić, Danijela and Mijatović, Sanja and Miljković, Đorđe and Harhaji-Trajković, Ljubica and Timotijević, Gordana S and Mojić, Marija and Dabideen, Darrin and Cheng, Kai Fan and McCubrey, James A and Mangano, Katia and Al-Abed, Yousef and Libra, Massimo and Garotta, Gianni and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2009",
abstract = "Application of the HIV protease inhibitor saquinavir (Saq) to cancer chemotherapy is limited by its numerous side effects. To overcome this toxicity, we modified the original compound by covalently attaching a nitric oxide (NO) group. We compared the efficacy of the parental and NO-modified drugs in vitro and in vivo. The novel compound saquinavir-NO (Saq-NO) significantly reduced the viability of a wide spectrum of human and rodent tumor cell lines at significantly lower concentration than the unmodified drug. In contrast to Saq, Saq-NO had no effect on the viability of primary cells and drastically reduced B16 melanoma growth in syngeneic C57BL/6 mice. In addition, at the equivalent of the 100% lethal dose of Saq, Saq-NO treatment caused no apparent signs of toxicity. Saq-NO blocked the proliferation of C6 and 1316 cells, up-regulated p53 expression, and promoted the differentiation of these two cell types into oligodendrocytes or Schwann-like cells, respectively. Although it has been well documented that Saq decreases tumor cell viability by inhibiting Akt, the anticancer properties of Saq-NO were completely independent of the phosphatidylinositol 3-kinase/Akt signaling pathway. Moreover, Saq-NO transiently up-regulated Akt phosphorylation, delivering a protective signal that could be relevant for primary cell protection and the absence of drug toxicity in vivo. It was unlikely that released NO was independently responsible for these drug effects because Saq-NO treatment increased intracellular and secreted NO levels only slightly. Rather, the chemical modification seems to have produced a qualitatively new chemical entity, which may have a unique mode of action against cancer cells. [Mol Cancer Ther 2009;8(5):1169-78]",
journal = "Molecular Cancer Therapeutics",
title = "The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt",
number = "5",
volume = "8",
pages = "1178",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1453"
}

Maksimović-Ivanić, D., Mijatović, S., Miljković, Đ., Harhaji-Trajković, L., Timotijević, G. S., Mojić, M., Dabideen, D., Cheng, K. F., McCubrey, J. A., Mangano, K., Al-Abed, Y., Libra, M., Garotta, G., Stošić-Grujičić, S.,& Nicoletti, F.. (2009). The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt. in Molecular Cancer Therapeutics, 8(5).
https://hdl.handle.net/21.15107/rcub_ibiss_1453

Maksimović-Ivanić D, Mijatović S, Miljković Đ, Harhaji-Trajković L, Timotijević GS, Mojić M, Dabideen D, Cheng KF, McCubrey JA, Mangano K, Al-Abed Y, Libra M, Garotta G, Stošić-Grujičić S, Nicoletti F. The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt. in Molecular Cancer Therapeutics. 2009;8(5):null-1178.
https://hdl.handle.net/21.15107/rcub_ibiss_1453 .

Maksimović-Ivanić, Danijela, Mijatović, Sanja, Miljković, Đorđe, Harhaji-Trajković, Ljubica, Timotijević, Gordana S, Mojić, Marija, Dabideen, Darrin, Cheng, Kai Fan, McCubrey, James A, Mangano, Katia, Al-Abed, Yousef, Libra, Massimo, Garotta, Gianni, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt" in Molecular Cancer Therapeutics, 8, no. 5 (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1453 .

TY  - JOUR
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Harhaji-Trajković, Ljubica
AU  - Miljković, Đorđe
AU  - Dabideen, Darrin
AU  - Cheng, Kai Fan
AU  - Mangano, Katia
AU  - Malaponte, Graziella
AU  - Ai-Abed, Yousef
AU  - Libra, Massimo
AU  - Garotta, Gianni
AU  - Nicoletti, Ferdinando
AU  - Stošić-Grujičić, Stanislava
PY  - 2008
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1543
AB  - Preclinical studies have shown that nitric oxide (NO)donating nonsteroidal anti-inflammatory drugs possess anticancer activities. Here, we report in vitro and in vivo studies showing the antitumor effect of the NO-donating isoxazole derivative (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid (GIT-27NO). GIT-27NO, but not the NO-deprived parental compound VGX-1027, significantly affected viability of both rodent (L929, B16, and C6) and human (U1251, BT20, HeLa, and LS174) tumor cell lines. GIT-27NO triggered either apoptotic cell death (e.g., L929 cells) or autophagic cell death (C6 and B16 cells). Moreover, GIT-27NO hampered the viability of cisplatin-resistant B16 cells. NO scavenger hemoglobin completely prevented GIT-27NO-induced death, indicating that NO release mediated the tumoricidal effect of the compound. Increase in intracellular NO upon on the treatment was associated with intensified production of reactive oxygen species, whereas their neutralization by antioxidant N-acetylcysteine resulted in partial recovery of cell viability. The antitumor activity of the drug was mediated by the selective activation of mitogen-activated protein kinases in a cell-specific manner and was neutralized by their specific inhibitors. In vivo treatment with GIT-27NO significantly reduced the B16 melanoma growth in syngeneic C57BL/6 mice. The therapeutic effect occurred at dose (0.5 mg/mouse) up to 160 times lower than those needed to induce acute lethality (80 mg/mouse). In addition, a dose of GIT-27NO five times higher than that found effective in the melanoma model was well tolerated by the mice when administered for 4 consecutive weeks. These data warrant additional studies to evaluate the possible translation of these findings to the clinical setting.
T2  - Molecular Cancer Therapeutics
T1  - Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo
IS  - 3
VL  - 7
DO  - 10.1158/1535-7163.MCT-07-2037
SP  - 510
EP  - 520
ER  - 

@article{
author = "Maksimović-Ivanić, Danijela and Mijatović, Sanja and Harhaji-Trajković, Ljubica and Miljković, Đorđe and Dabideen, Darrin and Cheng, Kai Fan and Mangano, Katia and Malaponte, Graziella and Ai-Abed, Yousef and Libra, Massimo and Garotta, Gianni and Nicoletti, Ferdinando and Stošić-Grujičić, Stanislava",
year = "2008",
abstract = "Preclinical studies have shown that nitric oxide (NO)donating nonsteroidal anti-inflammatory drugs possess anticancer activities. Here, we report in vitro and in vivo studies showing the antitumor effect of the NO-donating isoxazole derivative (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid (GIT-27NO). GIT-27NO, but not the NO-deprived parental compound VGX-1027, significantly affected viability of both rodent (L929, B16, and C6) and human (U1251, BT20, HeLa, and LS174) tumor cell lines. GIT-27NO triggered either apoptotic cell death (e.g., L929 cells) or autophagic cell death (C6 and B16 cells). Moreover, GIT-27NO hampered the viability of cisplatin-resistant B16 cells. NO scavenger hemoglobin completely prevented GIT-27NO-induced death, indicating that NO release mediated the tumoricidal effect of the compound. Increase in intracellular NO upon on the treatment was associated with intensified production of reactive oxygen species, whereas their neutralization by antioxidant N-acetylcysteine resulted in partial recovery of cell viability. The antitumor activity of the drug was mediated by the selective activation of mitogen-activated protein kinases in a cell-specific manner and was neutralized by their specific inhibitors. In vivo treatment with GIT-27NO significantly reduced the B16 melanoma growth in syngeneic C57BL/6 mice. The therapeutic effect occurred at dose (0.5 mg/mouse) up to 160 times lower than those needed to induce acute lethality (80 mg/mouse). In addition, a dose of GIT-27NO five times higher than that found effective in the melanoma model was well tolerated by the mice when administered for 4 consecutive weeks. These data warrant additional studies to evaluate the possible translation of these findings to the clinical setting.",
journal = "Molecular Cancer Therapeutics",
title = "Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo",
number = "3",
volume = "7",
doi = "10.1158/1535-7163.MCT-07-2037",
pages = "510-520"
}

Maksimović-Ivanić, D., Mijatović, S., Harhaji-Trajković, L., Miljković, Đ., Dabideen, D., Cheng, K. F., Mangano, K., Malaponte, G., Ai-Abed, Y., Libra, M., Garotta, G., Nicoletti, F.,& Stošić-Grujičić, S.. (2008). Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo. in Molecular Cancer Therapeutics, 7(3), 510-520.
https://doi.org/10.1158/1535-7163.MCT-07-2037

Maksimović-Ivanić D, Mijatović S, Harhaji-Trajković L, Miljković Đ, Dabideen D, Cheng KF, Mangano K, Malaponte G, Ai-Abed Y, Libra M, Garotta G, Nicoletti F, Stošić-Grujičić S. Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo. in Molecular Cancer Therapeutics. 2008;7(3):510-520.
doi:10.1158/1535-7163.MCT-07-2037 .

Maksimović-Ivanić, Danijela, Mijatović, Sanja, Harhaji-Trajković, Ljubica, Miljković, Đorđe, Dabideen, Darrin, Cheng, Kai Fan, Mangano, Katia, Malaponte, Graziella, Ai-Abed, Yousef, Libra, Massimo, Garotta, Gianni, Nicoletti, Ferdinando, Stošić-Grujičić, Stanislava, "Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo" in Molecular Cancer Therapeutics, 7, no. 3 (2008):510-520,
https://doi.org/10.1158/1535-7163.MCT-07-2037 . .

TY  - JOUR
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Mojić, Marija
AU  - Malaponte, Graziella
AU  - Libra, Massimo
AU  - Cardile, Vera
AU  - Miljković, Đorđe
AU  - Harhaji-Trajković, Ljubica
AU  - Dabideen, Darrin
AU  - Cheng, Kai Fan
AU  - Bevelacqua, Ylenia
AU  - Donia, Marco
AU  - Garotta, Gianni
AU  - Ai-Abed, Yousef
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2008
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1517
AB  - In this study we evaluated the effects of the new NO donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) on the A375 human melanoma cell line. Treatment with the drug led to concentration-dependent reduction of mitochondrial respiration and number of viable cells in cultures. Decreased cell viability correlated with release and internalization of NO and was neutralized by the extracellular scavenger hemoglobin. GIT-27NO neither influenced cell division nor induced accidental or autophagic cell death. Early signs of apoptosis were observed upon coculture with the drug, and resulting in marked accumulation of hypodiploid cells, suggesting that the induction of apoptosis is one primary mode of action of the compound in A375 cells. GIT-27NO significantly inhibited the expression of the transcription repressor and apoptotic resistant factor YY1 and, in parallel, augmented the presence of total p53. The capacity of GIT-27NO to induce p53-mediated apoptosis along with inhibition of YY1 repressor in A375 melanoma cells indicates that GIT-27NO possesses an important anti-cancer pharmacological profile. The findings suggest the potential therapeutic use of GIT-27NO in the clinical setting. (C) 2008 Elsevier Inc. All rights reserved.
T2  - Nitric Oxide-Biology and Chemistry
T1  - Novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) induces p53 mediated apoptosis in human A375 melanoma cells
IS  - 2
VL  - 19
EP  - 183
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1517
ER  - 

@article{
author = "Mijatović, Sanja and Maksimović-Ivanić, Danijela and Mojić, Marija and Malaponte, Graziella and Libra, Massimo and Cardile, Vera and Miljković, Đorđe and Harhaji-Trajković, Ljubica and Dabideen, Darrin and Cheng, Kai Fan and Bevelacqua, Ylenia and Donia, Marco and Garotta, Gianni and Ai-Abed, Yousef and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2008",
abstract = "In this study we evaluated the effects of the new NO donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) on the A375 human melanoma cell line. Treatment with the drug led to concentration-dependent reduction of mitochondrial respiration and number of viable cells in cultures. Decreased cell viability correlated with release and internalization of NO and was neutralized by the extracellular scavenger hemoglobin. GIT-27NO neither influenced cell division nor induced accidental or autophagic cell death. Early signs of apoptosis were observed upon coculture with the drug, and resulting in marked accumulation of hypodiploid cells, suggesting that the induction of apoptosis is one primary mode of action of the compound in A375 cells. GIT-27NO significantly inhibited the expression of the transcription repressor and apoptotic resistant factor YY1 and, in parallel, augmented the presence of total p53. The capacity of GIT-27NO to induce p53-mediated apoptosis along with inhibition of YY1 repressor in A375 melanoma cells indicates that GIT-27NO possesses an important anti-cancer pharmacological profile. The findings suggest the potential therapeutic use of GIT-27NO in the clinical setting. (C) 2008 Elsevier Inc. All rights reserved.",
journal = "Nitric Oxide-Biology and Chemistry",
title = "Novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) induces p53 mediated apoptosis in human A375 melanoma cells",
number = "2",
volume = "19",
pages = "183",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1517"
}

Mijatović, S., Maksimović-Ivanić, D., Mojić, M., Malaponte, G., Libra, M., Cardile, V., Miljković, Đ., Harhaji-Trajković, L., Dabideen, D., Cheng, K. F., Bevelacqua, Y., Donia, M., Garotta, G., Ai-Abed, Y., Stošić-Grujičić, S.,& Nicoletti, F.. (2008). Novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) induces p53 mediated apoptosis in human A375 melanoma cells. in Nitric Oxide-Biology and Chemistry, 19(2).
https://hdl.handle.net/21.15107/rcub_ibiss_1517

Mijatović S, Maksimović-Ivanić D, Mojić M, Malaponte G, Libra M, Cardile V, Miljković Đ, Harhaji-Trajković L, Dabideen D, Cheng KF, Bevelacqua Y, Donia M, Garotta G, Ai-Abed Y, Stošić-Grujičić S, Nicoletti F. Novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) induces p53 mediated apoptosis in human A375 melanoma cells. in Nitric Oxide-Biology and Chemistry. 2008;19(2):null-183.
https://hdl.handle.net/21.15107/rcub_ibiss_1517 .

Mijatović, Sanja, Maksimović-Ivanić, Danijela, Mojić, Marija, Malaponte, Graziella, Libra, Massimo, Cardile, Vera, Miljković, Đorđe, Harhaji-Trajković, Ljubica, Dabideen, Darrin, Cheng, Kai Fan, Bevelacqua, Ylenia, Donia, Marco, Garotta, Gianni, Ai-Abed, Yousef, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "Novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide (GIT-27NO) induces p53 mediated apoptosis in human A375 melanoma cells" in Nitric Oxide-Biology and Chemistry, 19, no. 2 (2008),
https://hdl.handle.net/21.15107/rcub_ibiss_1517 .