No-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cells
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 pre...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Society of Medical Biochemists of Serbia, Belgrade
2013-01-01
|
| Series: | Journal of Medical Biochemistry |
| Subjects: | |
| Online Access: | https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2013/1452-82581304406M.pdf |
| _version_ | 1818326628377296896 |
|---|---|
| author | Mijatović Sanja Pešić Milica Mojić Marija Banković Jasna Miljković Đorđe Fagone Paolo Mangano Katia Nicoletti Ferdinando Mccubrey James Tanić Nikola Maksimović-Ivanić Danijela |
| author_facet | Mijatović Sanja Pešić Milica Mojić Marija Banković Jasna Miljković Đorđe Fagone Paolo Mangano Katia Nicoletti Ferdinando Mccubrey James Tanić Nikola Maksimović-Ivanić Danijela |
| author_sort | Mijatović Sanja |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T12:03:24Z |
| format | Article |
| id | doaj.art-cca6833afc5f4c449de3a306cfc2ecd4 |
| institution | Directory Open Access Journal |
| issn | 1452-8258 1452-8266 |
| language | English |
| last_indexed | 2024-12-13T12:03:24Z |
| publishDate | 2013-01-01 |
| publisher | Society of Medical Biochemists of Serbia, Belgrade |
| record_format | Article |
| series | Journal of Medical Biochemistry |
| spelling | doaj.art-cca6833afc5f4c449de3a306cfc2ecd42022-12-21T23:47:02ZengSociety of Medical Biochemists of Serbia, BelgradeJournal of Medical Biochemistry1452-82581452-82662013-01-013244064161452-82581304406MNo-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cellsMijatović Sanja0Pešić Milica1Mojić Marija2Banković Jasna3Miljković Đorđe4Fagone Paolo5Mangano Katia6Nicoletti Ferdinando7Mccubrey James8Tanić Nikola9https://orcid.org/0000-0001-5817-7763Maksimović-Ivanić Danijela10https://orcid.org/0000-0002-8006-5079Department of Immunology, Institute for Biological Research 'Siniša Stanković', BelgradeDepartment of Immunology, Institute for Biological Research 'Siniša Stanković', BelgradeDepartment of Immunology, Institute for Biological Research 'Siniša Stanković', BelgradeDepartment of Immunology, Institute for Biological Research 'Siniša Stanković', BelgradeDepartment of Immunology, Institute for Biological Research 'Siniša Stanković', BelgradeDepartment of Bio-Medical Sciences, University of Catania, Catania, ItalyDepartment of Bio-Medical Sciences, University of Catania, Catania, ItalyDepartment of Bio-Medical Sciences, University of Catania, Catania, ItalyDepartment of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina, USAInstitute for Biological Research 'Siniša Stanković', BelgradeInstitute for Biological Research 'Siniša Stanković', BelgradeBackground: 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.https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2013/1452-82581304406M.pdfchemosensitizationnon-small cell lung carcinoma cellssaquinavirsaquinavir-notumor |
| spellingShingle | Mijatović Sanja Pešić Milica Mojić Marija Banković Jasna Miljković Đorđe Fagone Paolo Mangano Katia Nicoletti Ferdinando Mccubrey James Tanić Nikola Maksimović-Ivanić Danijela No-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cells Journal of Medical Biochemistry chemosensitization non-small cell lung carcinoma cells saquinavir saquinavir-no tumor |
| title | No-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cells |
| title_full | No-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cells |
| title_fullStr | No-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cells |
| title_full_unstemmed | No-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cells |
| title_short | No-modified saquinavir is equally efficient against doxorubicin sensitive and resistant non-small cell lung carcinoma cells |
| title_sort | no modified saquinavir is equally efficient against doxorubicin sensitive and resistant non small cell lung carcinoma cells |
| topic | chemosensitization non-small cell lung carcinoma cells saquinavir saquinavir-no tumor |
| url | https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2013/1452-82581304406M.pdf |
| work_keys_str_mv | AT mijatovicsanja nomodifiedsaquinavirisequallyefficientagainstdoxorubicinsensitiveandresistantnonsmallcelllungcarcinomacells AT pesicmilica nomodifiedsaquinavirisequallyefficientagainstdoxorubicinsensitiveandresistantnonsmallcelllungcarcinomacells AT mojicmarija nomodifiedsaquinavirisequallyefficientagainstdoxorubicinsensitiveandresistantnonsmallcelllungcarcinomacells AT bankovicjasna nomodifiedsaquinavirisequallyefficientagainstdoxorubicinsensitiveandresistantnonsmallcelllungcarcinomacells AT miljkovicđorđe nomodifiedsaquinavirisequallyefficientagainstdoxorubicinsensitiveandresistantnonsmallcelllungcarcinomacells AT fagonepaolo nomodifiedsaquinavirisequallyefficientagainstdoxorubicinsensitiveandresistantnonsmallcelllungcarcinomacells AT manganokatia nomodifiedsaquinavirisequallyefficientagainstdoxorubicinsensitiveandresistantnonsmallcelllungcarcinomacells AT nicolettiferdinando nomodifiedsaquinavirisequallyefficientagainstdoxorubicinsensitiveandresistantnonsmallcelllungcarcinomacells AT mccubreyjames nomodifiedsaquinavirisequallyefficientagainstdoxorubicinsensitiveandresistantnonsmallcelllungcarcinomacells AT tanicnikola nomodifiedsaquinavirisequallyefficientagainstdoxorubicinsensitiveandresistantnonsmallcelllungcarcinomacells AT maksimovicivanicdanijela nomodifiedsaquinavirisequallyefficientagainstdoxorubicinsensitiveandresistantnonsmallcelllungcarcinomacells |