title: Nitric oxide donor doxorubicins accumulate into Doxorubicin-resistant human colon cancer cells inducing cytotoxicity.
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.
authors.affiliation: Department of Drug Science and Technology, University of Turin , Via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Chegaev
authors.affiliation: Department of Genetics, Biology and Biochemistry, Turin School of Medicine, University of Turin , via Santena 5/bis, 10126 Torino, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Riganti
authors.affiliation: Department of Drug Science and Technology, University of Turin , Via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Loretta
authors.initials: L
authors.lastname: Lazzarato
authors.affiliation: Department of Drug Science and Technology, University of Turin , Via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rolando
authors.affiliation: Department of Drug Science and Technology, University of Turin , Via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Guglielmo
authors.affiliation: Department of Genetics, Biology and Biochemistry, Turin School of Medicine, University of Turin , via Santena 5/bis, 10126 Torino, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Campia
authors.affiliation: Department of Drug Science and Technology, University of Turin , Via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Fruttero
authors.affiliation: Department of Genetics, Biology and Biochemistry, Turin School of Medicine, University of Turin , via Santena 5/bis, 10126 Torino, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Bosia
authors.affiliation: Department of Drug Science and Technology, University of Turin , Via Pietro Giuria 9, 10125 Torino, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gasco
keywords: Multidrug resistance; P-glycoprotein; doxorubicin; nitric oxide