TY  - JOUR
AU  - Donia, Marco
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Mojić, Marija
AU  - Miljković, Đorđe
AU  - Timotijević, Gordana S
AU  - Fagone, Paolo
AU  - Caponnetto, Salvatore
AU  - Al-Abed, Yousef
AU  - McCubrey, James A
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1309
AB  - The NO-derivative of the HIV protease inhibitor saquinavir (Saq-NO) is a nontoxic variant of the parental drug with enhanced anticancer activity on several cell lines. However, it is still unclear whether the p53 status of the target cell might influence the sensitivity to Saq-NO. In this study we evaluated the in vitro and in vivo activity of Saq-NO on the p53-deficient hormone resistant prostate cancer PC-3 cells. We demonstrate that the absence of functional p53 is not essential for the capacity of Saq-NO to reduce prostate cancer cell growth. In contrast to its previously described cytostatic action in B16 and C6 cell lines, Saq-NO exerted cytotoxic effects in PC-3 cells leading to dominant induction of apoptosis and enhanced production of proapoptotic Bim. In addition, differently from saquinavir, Saq-NO restored TRAIL sensitivity that was correlated with increased expression of DR5 independent from ROS/RNS production and YY1 repression. NF kappa B activation may be responsible of the Saq-NO induced DR5 expression. Moreover, Saq-NO but not saquinavir, exerted synergistic activity with conventional cytostatic therapy. In agreement with these in vitro studies, Saq-NO inhibited the in vivo growth of PC-3 cells xenotransplants to a greater extent than the parental compound. Taken together, these data indicate that Saq-NO possesses powerful and suitable in vitro and in vivo chemotherapeutic potential to be further studied as a novel drug for the treatment of prostate cancer in the clinical setting.
T2  - Cell Cycle
T1  - In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the protease inhibitor saquinavir, on hormone resistant prostate cancer cells
IS  - 3
VL  - 10
EP  - 499
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1309
ER  - 

@article{
author = "Donia, Marco and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Mojić, Marija and Miljković, Đorđe and Timotijević, Gordana S and Fagone, Paolo and Caponnetto, Salvatore and Al-Abed, Yousef and McCubrey, James A and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2011",
abstract = "The NO-derivative of the HIV protease inhibitor saquinavir (Saq-NO) is a nontoxic variant of the parental drug with enhanced anticancer activity on several cell lines. However, it is still unclear whether the p53 status of the target cell might influence the sensitivity to Saq-NO. In this study we evaluated the in vitro and in vivo activity of Saq-NO on the p53-deficient hormone resistant prostate cancer PC-3 cells. We demonstrate that the absence of functional p53 is not essential for the capacity of Saq-NO to reduce prostate cancer cell growth. In contrast to its previously described cytostatic action in B16 and C6 cell lines, Saq-NO exerted cytotoxic effects in PC-3 cells leading to dominant induction of apoptosis and enhanced production of proapoptotic Bim. In addition, differently from saquinavir, Saq-NO restored TRAIL sensitivity that was correlated with increased expression of DR5 independent from ROS/RNS production and YY1 repression. NF kappa B activation may be responsible of the Saq-NO induced DR5 expression. Moreover, Saq-NO but not saquinavir, exerted synergistic activity with conventional cytostatic therapy. In agreement with these in vitro studies, Saq-NO inhibited the in vivo growth of PC-3 cells xenotransplants to a greater extent than the parental compound. Taken together, these data indicate that Saq-NO possesses powerful and suitable in vitro and in vivo chemotherapeutic potential to be further studied as a novel drug for the treatment of prostate cancer in the clinical setting.",
journal = "Cell Cycle",
title = "In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the protease inhibitor saquinavir, on hormone resistant prostate cancer cells",
number = "3",
volume = "10",
pages = "499",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1309"
}

Donia, M., Maksimović-Ivanić, D., Mijatović, S., Mojić, M., Miljković, Đ., Timotijević, G. S., Fagone, P., Caponnetto, S., Al-Abed, Y., McCubrey, J. A., Stošić-Grujičić, S.,& Nicoletti, F.. (2011). In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the protease inhibitor saquinavir, on hormone resistant prostate cancer cells. in Cell Cycle, 10(3).
https://hdl.handle.net/21.15107/rcub_ibiss_1309

Donia M, Maksimović-Ivanić D, Mijatović S, Mojić M, Miljković Đ, Timotijević GS, Fagone P, Caponnetto S, Al-Abed Y, McCubrey JA, Stošić-Grujičić S, Nicoletti F. In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the protease inhibitor saquinavir, on hormone resistant prostate cancer cells. in Cell Cycle. 2011;10(3):null-499.
https://hdl.handle.net/21.15107/rcub_ibiss_1309 .

Donia, Marco, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Mojić, Marija, Miljković, Đorđe, Timotijević, Gordana S, Fagone, Paolo, Caponnetto, Salvatore, Al-Abed, Yousef, McCubrey, James A, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "In vitro and in vivo anticancer action of Saquinavir-NO, a novel nitric oxide-derivative of the protease inhibitor saquinavir, on hormone resistant prostate cancer cells" in Cell Cycle, 10, no. 3 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1309 .

TY  - CONF
AU  - Donia, Marco
AU  - Mijatović, Sanja
AU  - Timotijević, Gordana S
AU  - Miljković, Đorđe
AU  - Stošić-Grujičić, Stanislava
AU  - Caponnetto, Salvatore
AU  - Fagone, Paolo
AU  - Mojić, Marija
AU  - Libra, Massimo
AU  - Maksimović-Ivanić, Danijela
AU  - Mangano, Katia
AU  - Nicoletti, Ferdinando
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1410
C3  - International Journal of Molecular Medicine
T1  - The effects of the nitric oxide-modified HIV protease inhibitor Saquinavir-NO (Saq-NO) on p53-deficient androgen independent prostate cancer cell lines
IS  - null
VL  - 26
EP  - S69
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1410
ER  - 

@conference{
author = "Donia, Marco and Mijatović, Sanja and Timotijević, Gordana S and Miljković, Đorđe and Stošić-Grujičić, Stanislava and Caponnetto, Salvatore and Fagone, Paolo and Mojić, Marija and Libra, Massimo and Maksimović-Ivanić, Danijela and Mangano, Katia and Nicoletti, Ferdinando",
year = "2010",
journal = "International Journal of Molecular Medicine",
title = "The effects of the nitric oxide-modified HIV protease inhibitor Saquinavir-NO (Saq-NO) on p53-deficient androgen independent prostate cancer cell lines",
number = "null",
volume = "26",
pages = "S69",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1410"
}

Donia, M., Mijatović, S., Timotijević, G. S., Miljković, Đ., Stošić-Grujičić, S., Caponnetto, S., Fagone, P., Mojić, M., Libra, M., Maksimović-Ivanić, D., Mangano, K.,& Nicoletti, F.. (2010). The effects of the nitric oxide-modified HIV protease inhibitor Saquinavir-NO (Saq-NO) on p53-deficient androgen independent prostate cancer cell lines. in International Journal of Molecular Medicine, 26(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1410

Donia M, Mijatović S, Timotijević GS, Miljković Đ, Stošić-Grujičić S, Caponnetto S, Fagone P, Mojić M, Libra M, Maksimović-Ivanić D, Mangano K, Nicoletti F. The effects of the nitric oxide-modified HIV protease inhibitor Saquinavir-NO (Saq-NO) on p53-deficient androgen independent prostate cancer cell lines. in International Journal of Molecular Medicine. 2010;26(null):null-S69.
https://hdl.handle.net/21.15107/rcub_ibiss_1410 .

Donia, Marco, Mijatović, Sanja, Timotijević, Gordana S, Miljković, Đorđe, Stošić-Grujičić, Stanislava, Caponnetto, Salvatore, Fagone, Paolo, Mojić, Marija, Libra, Massimo, Maksimović-Ivanić, Danijela, Mangano, Katia, Nicoletti, Ferdinando, "The effects of the nitric oxide-modified HIV protease inhibitor Saquinavir-NO (Saq-NO) on p53-deficient androgen independent prostate cancer cell lines" in International Journal of Molecular Medicine, 26, no. null (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1410 .