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 .