Acidosis affects tumor cell survival through modulation of nitric oxide release
2005
Аутори:
Harhaji-Trajković, LjubicaPopadić, Dušan
Miljković, Đorđe
Stojanović, Ivana D.
Isaković, Aleksandra
Trajković, Vladimir
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2005 Elsevier Inc.
Метаподаци
Приказ свих података о документуАпстракт:
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.
Кључне речи:
Cancer; PH; Acidosis; iNOS; Nitric oxide; Apoptosis; Necrosis; Free radicalsИзвор:
Free Radical Biology and Medicine, 2005, 40, 2, 226-235Финансирање / пројекти:
- Ministry of Science and Environmental Protection of the Republic of Serbia (Grants 1664 and 2020)
DOI: 10.1016/j.freeradbiomed.2005.08.027
ISSN: 0891-5849
PubMed: 16413405