TY  - JOUR
AU  - Harhaji-Trajković, Ljubica
AU  - Popadić, Dušan
AU  - Miljković, Đorđe
AU  - Stojanović, Ivana D.
AU  - Isaković, Aleksandra
AU  - Trajković, Vladimir
PY  - 2005
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6015
AB  - The influence of environmental pH on the production of tumoricidal free radical nitric oxide (NO) was investigated in mouse fibrosarcoma L929 and rat glioma C6 cell lines. A combination of IFN-gamma and IL-1 induced a significant NO release and subsequent reduction of cell viability in tumor cell lines. Acidification of cell culture medium reduced tumor cell NO production in a pH-dependent manner. While the inhibitory effect of acidosis on NO production in C6 cells was associated with a further decrease in cell viability, it completely rescued L929 cells from NO-dependent apoptotic and necrotic death. Acidic pH diminished IFN-gamma+ IL-1-induced expression of inducible NO synthase (iNOS) mRNA and protein, and abolished the activation of iNOS transcription factor IRF-1 in L929 cells. Moreover, extracellular acidosis significantly impaired cytokine-induced phosphorylation of MAP kinase p44/42 (ERK1/2) and subsequent expression of transcription factor c-Fos in L929 cells. Finally, mild acidosis (pH 6.8) augmented, while severe acidosis (pH 6.0) reduced, IFN-gamma-induced iNOS activation/NO release and NO-dependent anticancer activity of rat and mouse macrophages. Taken together, our findings indicate that modulation of macrophage and tumor cell iNOS by an acidic microenvironment might influence the progression of NO-sensitive solid tumors.
PB  - Elsevier Inc.
T2  - Free Radical Biology and Medicine
T1  - Acidosis affects tumor cell survival through modulation of nitric oxide release
IS  - 2
VL  - 40
DO  - 10.1016/j.freeradbiomed.2005.08.027
SP  - 226
EP  - 235
ER  - 

@article{
author = "Harhaji-Trajković, Ljubica and Popadić, Dušan and Miljković, Đorđe and Stojanović, Ivana D. and Isaković, Aleksandra and Trajković, Vladimir",
year = "2005",
abstract = "The influence of environmental pH on the production of tumoricidal free radical nitric oxide (NO) was investigated in mouse fibrosarcoma L929 and rat glioma C6 cell lines. A combination of IFN-gamma and IL-1 induced a significant NO release and subsequent reduction of cell viability in tumor cell lines. Acidification of cell culture medium reduced tumor cell NO production in a pH-dependent manner. While the inhibitory effect of acidosis on NO production in C6 cells was associated with a further decrease in cell viability, it completely rescued L929 cells from NO-dependent apoptotic and necrotic death. Acidic pH diminished IFN-gamma+ IL-1-induced expression of inducible NO synthase (iNOS) mRNA and protein, and abolished the activation of iNOS transcription factor IRF-1 in L929 cells. Moreover, extracellular acidosis significantly impaired cytokine-induced phosphorylation of MAP kinase p44/42 (ERK1/2) and subsequent expression of transcription factor c-Fos in L929 cells. Finally, mild acidosis (pH 6.8) augmented, while severe acidosis (pH 6.0) reduced, IFN-gamma-induced iNOS activation/NO release and NO-dependent anticancer activity of rat and mouse macrophages. Taken together, our findings indicate that modulation of macrophage and tumor cell iNOS by an acidic microenvironment might influence the progression of NO-sensitive solid tumors.",
publisher = "Elsevier Inc.",
journal = "Free Radical Biology and Medicine",
title = "Acidosis affects tumor cell survival through modulation of nitric oxide release",
number = "2",
volume = "40",
doi = "10.1016/j.freeradbiomed.2005.08.027",
pages = "226-235"
}

Harhaji-Trajković, L., Popadić, D., Miljković, Đ., Stojanović, I. D., Isaković, A.,& Trajković, V.. (2005). Acidosis affects tumor cell survival through modulation of nitric oxide release. in Free Radical Biology and Medicine
Elsevier Inc.., 40(2), 226-235.
https://doi.org/10.1016/j.freeradbiomed.2005.08.027

Harhaji-Trajković L, Popadić D, Miljković Đ, Stojanović ID, Isaković A, Trajković V. Acidosis affects tumor cell survival through modulation of nitric oxide release. in Free Radical Biology and Medicine. 2005;40(2):226-235.
doi:10.1016/j.freeradbiomed.2005.08.027 .

Harhaji-Trajković, Ljubica, Popadić, Dušan, Miljković, Đorđe, Stojanović, Ivana D., Isaković, Aleksandra, Trajković, Vladimir, "Acidosis affects tumor cell survival through modulation of nitric oxide release" in Free Radical Biology and Medicine, 40, no. 2 (2005):226-235,
https://doi.org/10.1016/j.freeradbiomed.2005.08.027 . .