Nitric Oxide Donor Doxorubicins Accumulate into Doxorubicin-Resistant Human Colon Cancer Cells Inducing Cytotoxicity
journal contributionposted on 14.07.2011, 00:00 by Konstantin Chegaev, Chiara Riganti, Loretta Lazzarato, Barbara Rolando, Stefano Guglielmo, Ivana Campia, Roberta Fruttero, Amalia Bosia, Alberto Gasco
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.
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mechanismHTdonor nitrooxyabilitydoxorubicinphenylsulfonyl furoxan moietiesconjugationcytotoxic effectcytotoxicitydrug effluxnitrationNitric Oxide Donor Doxorubicins Accumulateinhibitioncompoundnitric oxidetyrosine residuesPreliminary immunoblotting studiescolon cancer cellsInducingMRP 3 proteinHumanbehavior parallelsCytotoxicityProductnitrite