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
2011
Аутори
Donia, MarcoMaksimović-Ivanić, Danijela
Mijatović, Sanja
Mojić, Marija
Miljković, Djordje
Timotijević, Gordana
Fagone, Paolo
Caponnetto, Salvatore
Al-Abed, Yousef
McCubrey, James A.
Stošić-Grujičić, Stanislava
Nicoletti, Ferdinando
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
prostate cancer / nitric oxide modified saquinavir / immunosensitization / chemosenzitization / apoptosisИзвор:
Cell Cycle, 2011, 10, 3, 492-499Издавач:
- Taylor & Francis Inc, Philadelphia
Финансирање / пројекти:
- Физиолошка и фармаколошка модулација имуноинфламаторних и малигних болести (RS-MESTD-MPN2006-2010-143029)
DOI: 10.4161/cc.10.3.14727
ISSN: 1538-4101
WoS: 000286827100026
Scopus: 2-s2.0-79851501503
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Donia, Marco AU - Maksimović-Ivanić, Danijela AU - Mijatović, Sanja AU - Mojić, Marija AU - Miljković, Djordje AU - Timotijević, Gordana 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://imagine.imgge.bg.ac.rs/handle/123456789/487 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. PB - Taylor & Francis Inc, Philadelphia 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 EP - 499 IS - 3 SP - 492 VL - 10 DO - 10.4161/cc.10.3.14727 ER -
@article{ author = "Donia, Marco and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Mojić, Marija and Miljković, Djordje and Timotijević, Gordana 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.", publisher = "Taylor & Francis Inc, Philadelphia", 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", pages = "499-492", number = "3", volume = "10", doi = "10.4161/cc.10.3.14727" }
Donia, M., Maksimović-Ivanić, D., Mijatović, S., Mojić, M., Miljković, D., Timotijević, G., 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 Taylor & Francis Inc, Philadelphia., 10(3), 492-499. https://doi.org/10.4161/cc.10.3.14727
Donia M, Maksimović-Ivanić D, Mijatović S, Mojić M, Miljković D, Timotijević G, 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):492-499. doi:10.4161/cc.10.3.14727 .
Donia, Marco, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Mojić, Marija, Miljković, Djordje, Timotijević, Gordana, 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):492-499, https://doi.org/10.4161/cc.10.3.14727 . .