Modifikovana forma sakvinavira efikasno suprimira rast ćelija nesitnoćelijskog karcinoma pluća različite osetljivosti na doksorubicin
No-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cells
2013
Authors:
Mijatović, SanjaPešić, Milica
Mojić, Marija
Banković, Jasna
Miljković, Đorđe
Fagone, Paolo
Mangano, Katia
Nicoletti, Ferdinando
Mccubrey, James
Tanić, Nikola
Maksimović-Ivanić, Danijela
Document Type:
Article (Published version)
,
© 2013 by the Society of Medical Biochemists of Serbia
Metadata
Show full item recordAbstract:
Background: The NO-modified form of the HIV inhibitor saquinavir (Saq-NO) inhibited the growth of a variety of cancer cell lines in vitro and in vivo more potently than the original compound in a nontoxic fashion. In addition, chemo- and immunosensitizing properties were observed. The aim of the present study was to evaluate its anticancer action against non-small cell lung carcinoma cells in their doxorubicin (DOXO) sensitive and resistant phenotype (NCI-H460 and NCI-H460/R). Methods: The viability of cells was analyzed by MTT and crystal violet assays. DR5 expression was estimated by real time RT-PCR and flow cytometry. Activity of P-glycoprotein (P-gp) pumps was evaluated by the Rho123 accumulation assay. Results: Saq-NO diminished the viability of lung cancer cells through induction of cell cycle arrest in the G0/G1 phase independently of the overexpression of the P-gp pumps. In addition, Saq-NO elevated or completely reconstituted the doxorubicin efficacy in NCI-H460 and NCI-H460/R, respectively. The chemosensitizing effect in DOXO resistant cells was a consequence of P-gp inhibition which was found to be more potent than that observed with dex-verapamil, a conventional inhibitor of P-gp. Sensitization to DOXO upon Saq-NO was accompanied by elevated DR5 expression, but the resistance to TRAIL was not abrogated. Conclusions: The NO-modified HIV inhibitor saquinavir displayed equal antiproliferative and chemosensitizing properties in DOXO sensitive and resistant non-small cell lung carcinoma cells, suggesting the importance of the evaluation of this drug as an antineoplastic agent.
Keywords:
tumor; chemosensitization; non-small cell lung carcinoma cells; sakvinavir; saquinavir; sakvinavir-NO; nesitnoćelijski karcinom pluća; saquinavir-NO; tumor; hemosenzitizacijaSource:
Journal of Medical Biochemistry, 2013, 32, 4, 406-416
DOI: 10.2478/jomb-2013-0050
ISSN: 1452-8258