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2011 ; 2
(7
): 494-7
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Nitric oxide donor doxorubicins accumulate into Doxorubicin-resistant human colon
cancer cells inducing cytotoxicity
#MMPMID24900337
Chegaev K
; Riganti C
; Lazzarato L
; Rolando B
; Guglielmo S
; Campia I
; Fruttero R
; Bosia A
; Gasco A
ACS Med Chem Lett
2011[Jul]; 2
(7
): 494-7
PMID24900337
show ga
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.