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 language | English |
|---|---|
| Pages (from-to) | 3767-3771 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 64 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Jun 1 2004 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Nitric oxide confers therapeutic activity to dendritic cells in a mouse model of melanoma
AU - Perrotta, Cristiana
AU - Falcone, Sestina
AU - Capobianco, Annalisa
AU - Camporeale, Annalisa
AU - Sciorati, Clara
AU - De Palma, Clara
AU - Pisconti, Addolorata
AU - Rovere-Querini, Patrizia
AU - Bellone, Matteo
AU - Manfredi, Angelo A.
AU - Clementi, Emilio
PY - 2004/6/1
Y1 - 2004/6/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=2542562703&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2542562703&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-04-0668
DO - 10.1158/0008-5472.CAN-04-0668
M3 - Article
C2 - 15172982
AN - SCOPUS:2542562703
VL - 64
SP - 3767
EP - 3771
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 11
ER -