Nitric oxide (NO) release from a suitable NO photodonor (NOP) can be fine-tuned by visible light stimuli at doses that are not toxic to cells but that inhibit several efflux pumps; these are mainly responsible for the multidrug resistance of the anticancer agent doxorubicin (DOX). The strategy may thus increase DOX toxicity against resistant cancer cells. Moreover, a novel molecular hybrid covalently joining DOX and NOP showed similar increased toxicity toward resistant cancer cells and, in addition, lower cardiotoxicity than DOX. This opens new and underexplored approaches to overcoming the main therapeutic drawbacks of this chemotherapeutic based on light-controlled release of NO.

Light-Regulated NO Release as a Novel Strategy To Overcome Doxorubicin Multidrug Resistance

CHEGAEV, Konstantin;GAZZANO, Elena;ABDELRAHMAN, GAMALELDEIN FATHY ABDELLATEF;BLANGETTI, Marco;ROLANDO, Barbara;RIGANTI, Chiara;FRUTTERO, Roberta;GASCO, Alberto;Sortino, Salvatore
2017

Abstract

Nitric oxide (NO) release from a suitable NO photodonor (NOP) can be fine-tuned by visible light stimuli at doses that are not toxic to cells but that inhibit several efflux pumps; these are mainly responsible for the multidrug resistance of the anticancer agent doxorubicin (DOX). The strategy may thus increase DOX toxicity against resistant cancer cells. Moreover, a novel molecular hybrid covalently joining DOX and NOP showed similar increased toxicity toward resistant cancer cells and, in addition, lower cardiotoxicity than DOX. This opens new and underexplored approaches to overcoming the main therapeutic drawbacks of this chemotherapeutic based on light-controlled release of NO.
ACS MEDICINAL CHEMISTRY LETTERS
8
3
361
365
http://pubs.acs.org/toc/amclct
Doxorubicin; efflux pump inhibition; light; multidrug resistance; Nitric oxide
Chegaev, Konstantin; Fraix, Aurore; Gazzano, Elena; Abd Ellatef, Gamal Eldein F.; Blangetti, Marco; Rolando, Barbara; Conoci, Sabrina; Riganti, Chiara; Fruttero, Roberta; Gasco, Alberto; Sortino, Salvatore
File in questo prodotto:
File Dimensione Formato  
acsmedchemlett%2E7b00016.pdf

non disponibili

Descrizione: PDF editoriale
Tipo di file: PDF EDITORIALE
Dimensione 1.38 MB
Formato Adobe PDF
1.38 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Supporting_inf.pdf

accesso aperto

Descrizione: Parte supplementare
Tipo di file: MATERIALE NON BIBLIOGRAFICO
Dimensione 365.84 kB
Formato Adobe PDF
365.84 kB Adobe PDF Visualizza/Apri
Doxo_man_4aperto.pdf

embargo fino al 30/01/2019

Descrizione: Versione OA
Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 604.35 kB
Formato Adobe PDF
604.35 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1627517
Citazioni
  • ???jsp.display-item.citation.pmc??? 15
  • Scopus 37
  • ???jsp.display-item.citation.isi??? 33
social impact