No-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cells

• Main Authors: Mijatović Sanja, Pešić Milica, Mojić Marija, Banković Jasna, Miljković Đorđe, Fagone Paolo, Mangano Katia, Nicoletti Ferdinando, Mccubrey James, Tanić Nikola, Maksimović-Ivanić Danijela
• Format: Article
• Language: English
• Published: Society of Medical Biochemists of Serbia, Belgrade 2013-01-01
• Series: Journal of Medical Biochemistry
• Subjects: chemosensitization; non-small cell lung carcinoma cells; saquinavir; saquinavir-no; tumor
• Online Access: https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2013/1452-82581304406M.pdf
• ISSN: 1452-8258; 1452-8266

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.