Nitric oxide confers therapeutic activity to dendritic cells in a mouse model of melanoma

Cristiana Perrotta, Sestina Falcone, Annalisa Capobianco, Annalisa Camporeale, Clara Sciorati, Clara De Palma, Addolorata Pisconti, Patrizia Rovere-Querini, Matteo Bellone, Angelo A. Manfredi, Emilio Clementi

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3767-3771
Number of pages5
JournalCancer Research
Volume64
Issue number11
DOIs
Publication statusPublished - Jun 1 2004

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Dendritic Cells
DEET
Melanoma
Nitric Oxide
Neoplasms
Therapeutics
Apoptosis
Experimental Melanomas
Nitric Oxide Donors
Caspase 9
Mitochondrial Membrane Potential
T-Lymphocytes
Growth
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nitric oxide confers therapeutic activity to dendritic cells in a mouse model of melanoma. / Perrotta, Cristiana; Falcone, Sestina; Capobianco, Annalisa; Camporeale, Annalisa; Sciorati, Clara; De Palma, Clara; Pisconti, Addolorata; Rovere-Querini, Patrizia; Bellone, Matteo; Manfredi, Angelo A.; Clementi, Emilio.

In: Cancer Research, Vol. 64, No. 11, 01.06.2004, p. 3767-3771.

Research output: Contribution to journalArticle

Perrotta, Cristiana ; Falcone, Sestina ; Capobianco, Annalisa ; Camporeale, Annalisa ; Sciorati, Clara ; De Palma, Clara ; Pisconti, Addolorata ; Rovere-Querini, Patrizia ; Bellone, Matteo ; Manfredi, Angelo A. ; Clementi, Emilio. / Nitric oxide confers therapeutic activity to dendritic cells in a mouse model of melanoma. In: Cancer Research. 2004 ; Vol. 64, No. 11. pp. 3767-3771.
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AU - Manfredi, Angelo A.

AU - Clementi, Emilio

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AB - 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.

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