کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1940999 1050793 2006 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Desferrioxamine, an iron chelator, enhances HIF-1α accumulation via cyclooxygenase-2 signaling pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Desferrioxamine, an iron chelator, enhances HIF-1α accumulation via cyclooxygenase-2 signaling pathway
چکیده انگلیسی

Cyclooxygenase-2 (COX-2) is an important inducible enzyme in inflammation and is overexpressed in a variety of cancers. Evidence is rapidly accumulating that chronic inflammation may contribute to carcinogenesis through increase of cell proliferation, angiogenesis, and metastasis in a number of neoplasms, including colorectal carcinoma. In the present study, we investigated some mechanistic aspects of DFX-induced hypoxia-driven COX-2 expression. Desferrioxamine (DFX), an iron chelator, is known to upregulate inflammatory mediators. DFX induced the expression of COX-2 and accumulation of HIF-1α protein in dose-dependent manners, but hypoxia mimetic agent cobalt chloride (CoCl2) induced accumulation of HIF-1α protein but not increase of COX-2 expression. DFX-induced increase of COX-2 expression and HIF-1α protein level was attenuated by addition of ferric citrate. This result suggested that the iron chelating function of DFX was important to induce the increase of COX-2 and HIF-1α protein. PD98059 significantly inhibited the induction of COX-2 protein and accumulation of HIF-1α, suggesting that DFX-induced increase of HIF-1α and COX-2 protein was mediated, at least in part, through the ERK signaling pathway. In addition, pretreatment with NS-398 to inhibit COX-2 activity also effectively suppressed DFX-induced HIF-1α accumulation in human colon cancer cells, providing the evidence that COX-2 plays as a regulator of HIF-1α accumulation in DFX-treated colon cancer cells. Together, our findings suggest that iron metabolism may regulate stabilization of HIF-1α protein by modulating cyclooxygenase-2 signaling pathway.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 343, Issue 1, 28 April 2006, Pages 8–14
نویسندگان
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