TY  - JOUR
AU  - Tumino, Salvatore
AU  - Mojić, Marija
AU  - Dinić, Svetlana
AU  - Fagone, Paolo
AU  - Mangano, Katia
AU  - Maksimović-Ivanić, Danijela
AU  - Grdović, Nevena
AU  - Zocca, Mai-Britt
AU  - Miljković, Đorđe
AU  - Al-Abed, Yousef
AU  - Mijatović, Sanja
AU  - McCubrey, James A
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1199
AB  - We previously reported that the NO-modified form of HIV protease inhibitor Saquinavir ( Saq) is a potent antitumoral agent efficient against numerous tumor cell lines in vitro and in vivo. In acute toxicity studies, doses of Saq-NO equivalent to DL100 of the parental drug were completely nontoxic. Beside direct effect on malignant cell growth, Saq-NO sensitizes certain type of cells to tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL)-mediated cell death. In this study, we evaluated the effects of Saq-NO on androgen-dependent prostate cancer LNCaP. Saq-NO inhibited both the growth of LNCaP cells in vitro and in xenograft models. Suppression of tumor growth was accompanied with cell cycle arrest in G(0)/G(1) phase and established a persistent inhibition of proliferation. Furthermore, Saq-NO reverted sensitivity of LNCaP cells to TRAIL but not to TNF. Treatment of cells with Saq-NO induced transient upregulation of Akt and ERK1/2. This, however, did not represent the primary mode of action of Saq-NO, as elimination with specific inhibitors did not compromise the chemotherapic efficacy of the drug. However, permanent abrogation of phosphorylation of the S6 protein, which is the downstream target of both signaling pathways, was observed. Diminished S6 phosphorylation was associated with re-established sensitivity to TRAIL and reduction of X-linked inhibitor of apoptosis protein (XIAP). In summary, NO modification of Saq led to a new chemical entity with stronger and more pleiotropic antitumor activity than the parental drug.
T2  - Cell Cycle
T1  - Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL
IS  - 6
VL  - 11
EP  - 1182
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1199
ER  - 

@article{
author = "Tumino, Salvatore and Mojić, Marija and Dinić, Svetlana and Fagone, Paolo and Mangano, Katia and Maksimović-Ivanić, Danijela and Grdović, Nevena and Zocca, Mai-Britt and Miljković, Đorđe and Al-Abed, Yousef and Mijatović, Sanja and McCubrey, James A and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2012",
abstract = "We previously reported that the NO-modified form of HIV protease inhibitor Saquinavir ( Saq) is a potent antitumoral agent efficient against numerous tumor cell lines in vitro and in vivo. In acute toxicity studies, doses of Saq-NO equivalent to DL100 of the parental drug were completely nontoxic. Beside direct effect on malignant cell growth, Saq-NO sensitizes certain type of cells to tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL)-mediated cell death. In this study, we evaluated the effects of Saq-NO on androgen-dependent prostate cancer LNCaP. Saq-NO inhibited both the growth of LNCaP cells in vitro and in xenograft models. Suppression of tumor growth was accompanied with cell cycle arrest in G(0)/G(1) phase and established a persistent inhibition of proliferation. Furthermore, Saq-NO reverted sensitivity of LNCaP cells to TRAIL but not to TNF. Treatment of cells with Saq-NO induced transient upregulation of Akt and ERK1/2. This, however, did not represent the primary mode of action of Saq-NO, as elimination with specific inhibitors did not compromise the chemotherapic efficacy of the drug. However, permanent abrogation of phosphorylation of the S6 protein, which is the downstream target of both signaling pathways, was observed. Diminished S6 phosphorylation was associated with re-established sensitivity to TRAIL and reduction of X-linked inhibitor of apoptosis protein (XIAP). In summary, NO modification of Saq led to a new chemical entity with stronger and more pleiotropic antitumor activity than the parental drug.",
journal = "Cell Cycle",
title = "Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL",
number = "6",
volume = "11",
pages = "1182",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1199"
}

Tumino, S., Mojić, M., Dinić, S., Fagone, P., Mangano, K., Maksimović-Ivanić, D., Grdović, N., Zocca, M., Miljković, Đ., Al-Abed, Y., Mijatović, S., McCubrey, J. A., Stošić-Grujičić, S.,& Nicoletti, F.. (2012). Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL. in Cell Cycle, 11(6).
https://hdl.handle.net/21.15107/rcub_ibiss_1199

Tumino S, Mojić M, Dinić S, Fagone P, Mangano K, Maksimović-Ivanić D, Grdović N, Zocca M, Miljković Đ, Al-Abed Y, Mijatović S, McCubrey JA, Stošić-Grujičić S, Nicoletti F. Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL. in Cell Cycle. 2012;11(6):null-1182.
https://hdl.handle.net/21.15107/rcub_ibiss_1199 .

Tumino, Salvatore, Mojić, Marija, Dinić, Svetlana, Fagone, Paolo, Mangano, Katia, Maksimović-Ivanić, Danijela, Grdović, Nevena, Zocca, Mai-Britt, Miljković, Đorđe, Al-Abed, Yousef, Mijatović, Sanja, McCubrey, James A, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "Saquinavir-NO-targeted S6 protein mediates sensitivity of androgen-dependent prostate cancer cells to TRAIL" in Cell Cycle, 11, no. 6 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1199 .

TY  - JOUR
AU  - Donia, Marco
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Miljković, Đorđe
AU  - Mangano, Katia
AU  - Tumino, Salvatore
AU  - Biondi, Antonio
AU  - Basile, Francesco
AU  - Al-Abed, Yousef
AU  - Stošić-Grujičić, Stanislava
AU  - Nicoletti, Ferdinando
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1438
AB  - We investigated the effects of the recently synthetized NO donating agent GIT-27NO on the growth of human androgen independent and androgen dependent PC3 and LnCap cells xenografted in nude mice. We also tested the effects of GIT-27NO in the preclinical model of cell-mediated immunoinflammatory hepatitis that can be induced in mice by Concanavalin A (ConA) and that has been shown to benefit from the treatment with NO donating agents such as NO-aspirin. In agreement with in vitro data showing dose-dependent reduction of PO and LnCap cell viability with GIT-27NO, the i.p. treatment of mice xenografted with either of these cells with GIT-27NO significantly inhibited their growth as compared to the mice-treated with its vehicle. In addition, GIT-27NO given -24 and -1 h prior to e.v. challenge with 20 mg/kg ConA significantly suppressed the increase of transaminases that occurred 8 h after challenge in the control mice that received the vehicle. In addition, relative to these latter groups of mice, the histological signs of inflammatory hepatitis were markedly reduced in ConA-challenged mice that received GIT-27NO. In the hepatitis model, GIT-27NO was equally effective in preventing ConA-induced hepatitis regardless of whether it was administered intra peritoneally or per os. These data confirm that Grr-27NO is a powerful anticancer agent also endowed with pharmacological properties to prevent the development of cell-mediated murine immunoinflammatory hepatitis. (C) 2009 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis
IS  - 1-3
VL  - 615
EP  - 233
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1438
ER  - 

@article{
author = "Donia, Marco and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Miljković, Đorđe and Mangano, Katia and Tumino, Salvatore and Biondi, Antonio and Basile, Francesco and Al-Abed, Yousef and Stošić-Grujičić, Stanislava and Nicoletti, Ferdinando",
year = "2009",
abstract = "We investigated the effects of the recently synthetized NO donating agent GIT-27NO on the growth of human androgen independent and androgen dependent PC3 and LnCap cells xenografted in nude mice. We also tested the effects of GIT-27NO in the preclinical model of cell-mediated immunoinflammatory hepatitis that can be induced in mice by Concanavalin A (ConA) and that has been shown to benefit from the treatment with NO donating agents such as NO-aspirin. In agreement with in vitro data showing dose-dependent reduction of PO and LnCap cell viability with GIT-27NO, the i.p. treatment of mice xenografted with either of these cells with GIT-27NO significantly inhibited their growth as compared to the mice-treated with its vehicle. In addition, GIT-27NO given -24 and -1 h prior to e.v. challenge with 20 mg/kg ConA significantly suppressed the increase of transaminases that occurred 8 h after challenge in the control mice that received the vehicle. In addition, relative to these latter groups of mice, the histological signs of inflammatory hepatitis were markedly reduced in ConA-challenged mice that received GIT-27NO. In the hepatitis model, GIT-27NO was equally effective in preventing ConA-induced hepatitis regardless of whether it was administered intra peritoneally or per os. These data confirm that Grr-27NO is a powerful anticancer agent also endowed with pharmacological properties to prevent the development of cell-mediated murine immunoinflammatory hepatitis. (C) 2009 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis",
number = "1-3",
volume = "615",
pages = "233",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1438"
}

Donia, M., Mijatović, S., Maksimović-Ivanić, D., Miljković, Đ., Mangano, K., Tumino, S., Biondi, A., Basile, F., Al-Abed, Y., Stošić-Grujičić, S.,& Nicoletti, F.. (2009). The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis. in European Journal of Pharmacology, 615(1-3).
https://hdl.handle.net/21.15107/rcub_ibiss_1438

Donia M, Mijatović S, Maksimović-Ivanić D, Miljković Đ, Mangano K, Tumino S, Biondi A, Basile F, Al-Abed Y, Stošić-Grujičić S, Nicoletti F. The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis. in European Journal of Pharmacology. 2009;615(1-3):null-233.
https://hdl.handle.net/21.15107/rcub_ibiss_1438 .

Donia, Marco, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Miljković, Đorđe, Mangano, Katia, Tumino, Salvatore, Biondi, Antonio, Basile, Francesco, Al-Abed, Yousef, Stošić-Grujičić, Stanislava, Nicoletti, Ferdinando, "The novel NO-donating compound GIT-27NO inhibits in vivo growth of human prostate cancer cells and prevents murine immunoinflammatory hepatitis" in European Journal of Pharmacology, 615, no. 1-3 (2009),
https://hdl.handle.net/21.15107/rcub_ibiss_1438 .