Nitric oxide confers therapeutic activity to dendritic cells in a mouse model of melanoma.
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.
Perrotta
Cristiana
C
Department of Pharmaco-Biology, University of Calabria, Rende.
Falcone
Sestina
S
Capobianco
Annalisa
A
Camporeale
Annalisa
A
Sciorati
Clara
C
De Palma
Clara
C
Pisconti
Addolorata
A
Rovere-Querini
Patrizia
P
Bellone
Matteo
M
Manfredi
Angelo A
AA
Clementi
Emilio
E
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
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