The NO-modified HIV protease inhibitor as a valuable drug for hematological malignancies: Role of p70S6K
2015
Аутори:
Maksimović-Ivanić, DanijelaMojić, Marija
Bulatović, Mirna Z.
Radojkovic, Milica
Kuzmanovic, Milos
Ristic, Slobodan
Stošić-Grujičić, Stanislava
Miljković, Đorđe
Cavalli, Eugenio
Libra, Massimo
Fagone, Paolo
McCubrey, James
Nicoletti, Ferdinando
Mijatović, Sanja
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2015 Elsevier Ltd.
Метаподаци
Приказ свих података о документуАпстракт:
Covalent attachment of NO to the first approved HIV protease inhibitor
Saquinavir (Saq-NO) expands the therapeutic potential of the original
drug. Apart from retained antiviral activity, the modified drug exerts
strong antitumor effects and lower toxicity. In the present study, we
have evaluated the sensitivity of different hematological malignancies
to Saq-NO. Saq-NO efficiently diminished the viability of Jurkat, Raji,
HL-60 and K562 cells. While Jurkat and Raji cells (established from
pediatric patients) displayed abrogated proliferative potential, HL-60
and K652 cells (originated from adults) exposed to Saq-NO treatment
underwent caspase dependent apoptosis. In addition, similar sensitivity
to Saq-NO was observed in mononuclear blood cells obtained from
pediatric patients with acute lymphoblastic leukemia (ALL) and adult
patients with acute myeloid leukemia (AML). Western blot analysis
indicated p70S6 kinase as a possible intracellular target of Saq-NO
action. Moreover, the addition of a NO moiety to Lopinavir resulted in
improved antitumor potential as compared to the parental compound,
suggesting that NO-derived HIV protease inhibitors are a potential new
source of anticancer drugs with unique mode of action. (C) 2015 Elsevier
Ltd. All rights reserved.
Кључне речи:
Saquinavir; Saquinavir-NO; Acute lymphoid leukemia; Acute myeloid leukemia; p70S6 kinaseИзвор:
Leukemia Research, 2015, 39, 10, 1088-1095
DOI: 10.1016/j.leukres.2015.06.013
ISSN: 1873-5835