Products 4 and 5, obtained by conjugation of doxorubicin with nitric oxide (NO) donor nitrooxy and phenylsulfonyl furoxan moieties, respectively, accumulate in doxorubicin-resistant human colon cancer cells (HT29-dx), inducing high cytotoxicity. This behavior parallels the ability of the compounds to generate NO, detected as nitrite, in these cells. Preliminary immunoblotting studies suggest that the mechanism that underlies the cytotoxic effect could involve inhibition of cellular drug efflux due to nitration of tyrosine residues of the MRP3 protein pump.

Nitric Oxide Donor Doxorubicins Accumulate into Doxorubicin-Resistant Human Colon Cancer Cells Inducing Cytotoxicity

CHEGAEV, Konstantin;RIGANTI, Chiara;LAZZARATO, Loretta;ROLANDO, Barbara;GUGLIELMO, Stefano;CAMPIA, IVANA;FRUTTERO, Roberta;BOSIA, Amalia;GASCO, Alberto
2011

Abstract

Products 4 and 5, obtained by conjugation of doxorubicin with nitric oxide (NO) donor nitrooxy and phenylsulfonyl furoxan moieties, respectively, accumulate in doxorubicin-resistant human colon cancer cells (HT29-dx), inducing high cytotoxicity. This behavior parallels the ability of the compounds to generate NO, detected as nitrite, in these cells. Preliminary immunoblotting studies suggest that the mechanism that underlies the cytotoxic effect could involve inhibition of cellular drug efflux due to nitration of tyrosine residues of the MRP3 protein pump.
ACS MEDICINAL CHEMISTRY LETTERS
2
7
494
497
http://pubs.acs.org/journal/amclct
Multidrug resistance; doxorubicin; nitric oxide; P-glycoprotein
Konstantin Chegaev; Chiara Riganti; Loretta Lazzarato; Barbara Rolando; Stefano Guglielmo; Ivana Campia; Roberta Fruttero; Amalia Bosia; Alberto Gasco
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/88039
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