title: Nitric oxide confers therapeutic activity to dendritic cells in a mouse model of melanoma.
abstract: Susceptibility of dendritic cells (DCs) to tumor-induced apoptosis reduces their efficacy in cancer therapy. Here we show that delivery within exponentially growing B16 melanomas of DCs treated ex vivo with nitric oxide (NO), released by the NO donor (z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO), significantly reduced tumor growth, with cure of 37% of animals. DETA-NO-treated DCs became resistant to tumor-induced apoptosis because DETA-NO prevented tumor-induced changes in the expression of Bcl-2, Bax, and Bcl-xL; activation of caspase-9; and a reduction in the mitochondrial membrane potential. DETA-NO also increased DC cytotoxic activity against tumor cells and DC ability to trigger T-lymphocyte proliferation. All of the effects of DETA-NO were mediated through cGMP generation. NO and NO-generating drugs may therefore be used to increase the anticancer efficacy of DCs.
authors.affiliation: Department of Pharmaco-Biology, University of Calabria, Rende.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Perrotta
authors.forename: Sestina
authors.initials: S
authors.lastname: Falcone
authors.forename: Annalisa
authors.initials: A
authors.lastname: Capobianco
authors.forename: Annalisa
authors.initials: A
authors.lastname: Camporeale
authors.forename: Clara
authors.initials: C
authors.lastname: Sciorati
authors.forename: Clara
authors.initials: C
authors.lastname: De Palma
authors.forename: Addolorata
authors.initials: A
authors.lastname: Pisconti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rovere-Querini
authors.forename: Matteo
authors.initials: M
authors.lastname: Bellone
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
authors.forename: Emilio
authors.initials: E
authors.lastname: Clementi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D004789:Enzyme Activation; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007959:Lymphocyte Culture Test, Mixed; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D014226:Triazenes / Q000494:pharmacology
chemical_list: C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D020030:Nitric Oxide Donors; D014226:Triazenes; D009569:Nitric Oxide; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases; D006152:Cyclic GMP