English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Summary Background: The NO-modified form of the HIV inhibitor saquinavir (Saq-NO) inhibited the growth of a variety of can- cer cell lines in vitro and in vivo more potently than the orig- inal 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 doxoru- bicin (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 Gq/G1 phase in- dependently 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, respec- tively. 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 con- ventional 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 dis- played equal antiproliferative and chemosensitizing proper- ties in DOXO sensitive and resistant non-small cell lung car- cinoma cells, suggesting the importance of the evaluation of this drug as an antineoplastic agent. Kratak sadržaj Uvod: Inhibitor HIV proteaze- sakvinavir nakon modifikaci- je kovalentnim vezivanjem NO (Saq-NO) gubi toksična svoj- stva dok potentnije od originalnog jedinjenja inhibira in vitro i in vivo rast brojnih čelijskih linija kancera. Pored direktnog antitumorskog delovanja, Saq-NO povečava osetljivost čelija kancera na antitumorski imunski odgovor i konvencionalnu hemioterapiju. Ova študija je imala za cilj ispitivanje antitu- morskog potencijala Saq-NO na čelijskim linijama nesitno- čelijskog karcinoma pluča, senzitivnim (NCI-H460), odnos- no rezistentnim (NCI-H460/R) na doksorubicin. Metode: Vijabilitet čelija je evaluiran testovima MTT i »kristal violet«. Ekspresija receptora DR5 je procenjivana metodom RT-PCR u reálnom vremenu i protočnom citofluorimetrijom. Aktivnost P-gp pumpi odredivana je akumulacionim testom Rho123. Rezultati: Saq-NO inhibira rast čelija kancera pluča zausta- vljanjem čelija u fazi Gq/G^ čelijskog ciklusa a zapaženi efe- kat nije oslabljen povečanjem ekspresije P-gp pumpi. Pored toga, Saq-NO povečava osetljivost NCI-H460 čelija, dok u slučaju rezistentne forme, NCI-H460/R, potpuno rekonstituiše njihovu osetljivost na doksorubicin. Efekat hemosenziti- zacije je posledica inhibicije P-gp pumpi, što Saq-NO čini potentnijim od deksverapamila, uobičajenog inhibitora P-gp. Opisani fenomen je pračen povečanjem ekspresije receptora DR5 na genskom i membranskom nivou, ali time rezistencija na molekul TRAIL nije ukinuta. Zaključak: Saq-NO pokazuje značajan antiproliferativan i hemosenzitizujuči potencijal na čelijama nesitnočelijskog kancera pluča nezavisno od njihove osetljivosti odnosno rezistencije na doksorubicin, ukazujuči na potrebu daljeg ispitivanja ovog jedinjenja u svojstvu potencijalnog antineo- plastičnog agensa.

journal of medical biochemistry

No-Modified Saquinavir is Equally Efficient Against Doxorubicin Sensitive and Resistant Non-Small Cell Lung Carcinoma Cells / MODIFIKOVANA KOVANA FORMA SAKVINAVIRA EFIKASNO SU PRIMI RA RAST ĆELIJA NESITNOĆELIJSKOG KARCINOMA PLUĆA RAZLIČITE OSETUIVOSTI NA DOKSORUBICIN