TY  - JOUR
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Timotijević, Gordana
AU  - Miljković, Djordje
AU  - Donia, Marco
AU  - Libra, Massimo
AU  - Coco, Marinella
AU  - McCubrey, James
AU  - Al-Abed, Yousef
AU  - Korac, Aleksandra
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2010
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/434
AB  - The new chemical entity GIT-27NO was created by the covalent linkage of a NO moiety to the antiinflammatory isoxazoline VGX-1027 The compound has been shown to possess powerful anticancer effects both in vitro and in vivo However, its effects on nonsolid and metastatic forms of tumors have not yet been investigated We have studied the effects of GIT-27NO on the highly invasive mouse mammary TA3Ha cell line in vitro and in vivo In contrast to the conventional exogenous NO donor sodium nitroprusside, GIT-27NO successfully enhanced intracellular NO concentration in TA3Ha cells Intracellular accumulation of NO was followed by marked decrease in TA3Ha cell viability accompanied by typical apoptotic features Interestingly, inverted membrane phosphatidylserine residues. reduced volume of nucleus, condensed chromatin, and terminal fragmentation of DNA were associated with inhibited caspase-3 activity and transcription of the genes encoding caspase-3, -8, and -9 In parallel, GIT-27NO rapidly but transiently prevented the loss of p53 through phosphorylation on Ser 20 and provided the necessary signals tor the execution of downstream processes without p53 de novo synthesis The caspase-independent apoptotic-like death process triggered by GIT-27NO could be mediated by markedly down-regulated expression of the antiapoptotic Bcl-2 molecule observed in TA3Ha cells exposed to GIT-27NO In agreement with these in vitro data, GIT-27NO efficiently suppressed the growth of the ascites form and associated-lethality of tumor induced by TA3Ha cells in mice
PB  - Elsevier Science Inc, New York
T2  - Free Radical Biology and Medicine
T1  - Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO
EP  - 1099
IS  - 8
SP  - 1090
VL  - 48
DO  - 10.1016/j.freeradbiomed.2010.01.026
ER  - 

@article{
author = "Mijatović, Sanja and Maksimović-Ivanić, Danijela and Timotijević, Gordana and Miljković, Djordje and Donia, Marco and Libra, Massimo and Coco, Marinella and McCubrey, James and Al-Abed, Yousef and Korac, Aleksandra and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2010",
abstract = "The new chemical entity GIT-27NO was created by the covalent linkage of a NO moiety to the antiinflammatory isoxazoline VGX-1027 The compound has been shown to possess powerful anticancer effects both in vitro and in vivo However, its effects on nonsolid and metastatic forms of tumors have not yet been investigated We have studied the effects of GIT-27NO on the highly invasive mouse mammary TA3Ha cell line in vitro and in vivo In contrast to the conventional exogenous NO donor sodium nitroprusside, GIT-27NO successfully enhanced intracellular NO concentration in TA3Ha cells Intracellular accumulation of NO was followed by marked decrease in TA3Ha cell viability accompanied by typical apoptotic features Interestingly, inverted membrane phosphatidylserine residues. reduced volume of nucleus, condensed chromatin, and terminal fragmentation of DNA were associated with inhibited caspase-3 activity and transcription of the genes encoding caspase-3, -8, and -9 In parallel, GIT-27NO rapidly but transiently prevented the loss of p53 through phosphorylation on Ser 20 and provided the necessary signals tor the execution of downstream processes without p53 de novo synthesis The caspase-independent apoptotic-like death process triggered by GIT-27NO could be mediated by markedly down-regulated expression of the antiapoptotic Bcl-2 molecule observed in TA3Ha cells exposed to GIT-27NO In agreement with these in vitro data, GIT-27NO efficiently suppressed the growth of the ascites form and associated-lethality of tumor induced by TA3Ha cells in mice",
publisher = "Elsevier Science Inc, New York",
journal = "Free Radical Biology and Medicine",
title = "Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO",
pages = "1099-1090",
number = "8",
volume = "48",
doi = "10.1016/j.freeradbiomed.2010.01.026"
}

Mijatović, S., Maksimović-Ivanić, D., Timotijević, G., Miljković, D., Donia, M., Libra, M., Coco, M., McCubrey, J., Al-Abed, Y., Korac, A., Stošić-Grujičić, S.,& Nicoletti, F.. (2010). Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO. in Free Radical Biology and Medicine
Elsevier Science Inc, New York., 48(8), 1090-1099.
https://doi.org/10.1016/j.freeradbiomed.2010.01.026

Mijatović S, Maksimović-Ivanić D, Timotijević G, Miljković D, Donia M, Libra M, Coco M, McCubrey J, Al-Abed Y, Korac A, Stošić-Grujičić S, Nicoletti F. Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO. in Free Radical Biology and Medicine. 2010;48(8):1090-1099.
doi:10.1016/j.freeradbiomed.2010.01.026 .

Mijatović, Sanja, Maksimović-Ivanić, Danijela, Timotijević, Gordana, Miljković, Djordje, Donia, Marco, Libra, Massimo, Coco, Marinella, McCubrey, James, Al-Abed, Yousef, Korac, Aleksandra, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "Induction of caspase-independent apoptotic-like cell death of mouse mammary tumor TA3Ha cells in vitro and reduction of their lethality in vivo by the novel chemotherapeutic agent GIT-27NO" in Free Radical Biology and Medicine, 48, no. 8 (2010):1090-1099,
https://doi.org/10.1016/j.freeradbiomed.2010.01.026 . .

TY  - JOUR
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Miljković, Djordje
AU  - Harhaji-Trajković, Ljubica
AU  - Timotijević, Gordana
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://imagine.imgge.bg.ac.rs/handle/123456789/357
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]
PB  - Amer Assoc Cancer Research, Philadelphia
T2  - Molecular Cancer Therapeutics
T1  - The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt
EP  - 1178
IS  - 5
SP  - 1169
VL  - 8
DO  - 10.1158/1535-7163.MCT-08-0998
ER  - 

@article{
author = "Maksimović-Ivanić, Danijela and Mijatović, Sanja and Miljković, Djordje and Harhaji-Trajković, Ljubica and Timotijević, Gordana 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]",
publisher = "Amer Assoc Cancer Research, Philadelphia",
journal = "Molecular Cancer Therapeutics",
title = "The antitumor properties of a nontoxic, nitric oxide-modified version of saquinavir are independent of Akt",
pages = "1178-1169",
number = "5",
volume = "8",
doi = "10.1158/1535-7163.MCT-08-0998"
}

Maksimović-Ivanić, D., Mijatović, S., Miljković, D., Harhaji-Trajković, L., Timotijević, G., 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
Amer Assoc Cancer Research, Philadelphia., 8(5), 1169-1178.
https://doi.org/10.1158/1535-7163.MCT-08-0998

Maksimović-Ivanić D, Mijatović S, Miljković D, Harhaji-Trajković L, Timotijević G, 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):1169-1178.
doi:10.1158/1535-7163.MCT-08-0998 .

Maksimović-Ivanić, Danijela, Mijatović, Sanja, Miljković, Djordje, Harhaji-Trajković, Ljubica, Timotijević, Gordana, 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):1169-1178,
https://doi.org/10.1158/1535-7163.MCT-08-0998 . .